REPORT

Separation of Binary Mixture By Using Pervaporation
Chapter 1
INTRODUCTION TO PERVAPORATION
1.1 BACKGROUND:
Compared with traditional separation processes, such as distillation, extraction

and filtration, membrane technology is a relatively new method that has been developed
in the past few decades, but it has been widely adopted in many industries. The
membrane processes have the following distinguishing characteristics [Mulder 1991]:
1) Continuity and simplicity of the processes,
2) Adjustability of the separation properties,
3) Feasibility of incorporation into hybrid processes,
4) Low energy consumption and moderate operating conditions.
Developments in membrane formation techniques and materials
science accelerate the research and applications of membrane
technology. Now commercial membrane applications have successfully
displaced some conventional processes, and membrane technology
has become an indispensable component in many industrial fields and
our daily life.
Figure 1.1 Schematic membrane separation processes
Figure 1.1 shows a schematic membrane process [Mulder 1991;

Baker 2004]. Separation membranes are located between the feed
side and the permeate side. In most membrane processes, such as gas
separation, reverse osmosis and ultra filtration, both the feed and the
permeate sides are in the same phases, gas or liquid, while in
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pervaporation, the liquid feed is separated into vaporous permeates

with the aid of vacuum or a purge gas in the downstream side.
Pervaporation has become a very important technique to separate azeotropes, close-

boiling mixtures, and recover volatile organic chemicals from liquid mixtures, and now it
has emerged as a good choice for separating heat sensitive products. The phenomenon of
pervaporation was first discovered in 1917 by Kober [1995], but no extensive research
was carried out until in the 1950s by Binning et al. [1961].
In pervaporation processes with functional polymer membranes,
the non-porous dense membranes are essential. By choosing proper
membranes, pervaporation has great advantages as an alternative
separation method in the following separation tasks:
1) Dehydration of organic solvents,
2) Removal of organics from water,
3) Separation of organic liquids.
Non-porous dense membranes can also be applied in other separation
processes such as gas separation. Furthermore, both gas separation
and pervaporation can be interpreted with the solution diffusion
mechanism for mass transport in membranes. Membrane-based
pervaporation or vapor permeation is a promising alternative to
distillation since it is an energy-saving one-step separation process. If
the proper membrane material is selected, pervaporation can separate
azeotropic mixtures and close boiling mixtures that traditional
distillation has difficulties in processing [3].
1.2 MEMBRANE BASED PERVAPORATION SEPARATION:

Pervaporation, in its simplest form, is an energy efficient combination of
membrane permeation and evaporation. Liquid mixtures can be separated by partial
vaporization through a non-porus permselective membrane. This technique, which was
originally called “Liquid permeation” has subsequently been termed “pervaporation” in
order to emphasized the fact that permeate undergoes a phase change, from liquid to
vapor, during the transport through the barrier.
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It's considered an attractive alternative to other separation methods for a variety of

processes. For example, with the low temperatures and pressures involved in
pervaporation, it often has cost and performance advantages for the separation of
constant-boiling azeotropes. Pervaporation is also used for the dehydration of organic
solvents and the removal of organics from aqueous streams. Additionally, pervaporation
has emerged as a good choice for separation heat sensitive products. Pervaporation
involves the separation of two or more components across a membrane by differing rates
of diffusion through a thin polymer and an evaporative phase change comparable to a
simple flash step. A concentrate and vapor pressure gradient is used to allow one
component to preferentially permeate across the membrane. A vacuum applied to the
permeate side is coupled with the immediate condensation of the permeated vapors.
Pervaporation is typically suited to separating a minor component of a liquid mixture,
thus high selectivity through the membrane is essential.
Figure 1.2 Overview of Pervaporation process
In addition, a pervaporation unit can be integrated into a bioreactor to improve

bioconversion rate and reduce downstream processing costs, if membranes can
selectively remove volatile inhibitory substances from fermentation broths [7]. Compared
to the relatively easy separation of non-aggressive chemicals from water in industry, very
few commercial systems have been developed to separate aggressive organics-water
systems [8-11]. The most significant opportunity to use pervaporation is in splitting an
azeotrope or a close boiling-temperature mixture, where distillation is less efficient due to
the huge amount of energy consumption. Theoretically, if a liquid feed contacts a
nonporous membrane with vacuum downstream, the vaporization rate of each component
in the liquid is limited by the membrane permeability. In other words, the concentration
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distribution of each component in the liquid and vapor is not only controlled by the
thermodynamic equilibrium [12], but also is governed by the membrane permeability. In
this case, the membrane is sometimes referred to as a “mass separating agent”.
Nevertheless, the membrane-mediated evaporation is generally regarded as
pervaporation. In order to maximize the driving force, i.e. an activity difference between
a feed liquid and permeate vapor, heating the feed liquid at the boiling temperature on
one side of the membrane and pulling a vacuum or cooling the permeate vapor to
condense on the other side are generally applied in the pervaporation process [3].
Figure 1.2.1: Membrane-based pervaporation separation processes Vacuum

Operation
Pervaporation can used for breaking azeotropes, dehydration of solvents and other
volatile organics, organic/organic separations such as ethanol or methanol removal, and
wastewater purification.
Characteristics of the pervaporation process include:
1. Low energy consumption
2. No entrainer required, no contamination
3. Permeate must be volatile at operating conditions
4. Functions independent of vapor/liquid equilibrium
1.2.1
1.3 MEMBRANE MATERIAL:
Tobacco plants require fertile well-drained moist soil and warm temperatures.
Most types of tobacco are grown in full sun to counteract these problems; tobacco
farmers grow strains of tobacco that resist disease and insects. By rotating crops (planting
tobacco one year and different crop in the same field next year i.e. change of crop
successively) farmers keep the population of tobacco pests in check by depraving them of
tobacco plants on alternate years.
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The right stage for harvesting tobacco crop is when the leaves are mature. In
tobacco, generally lower leaves mature first and then the upper leaves in regular
ascending order. In India a number of tobaccos such as cigar tobacco, chewing tobacco,
natu tobacco, hookah tobacco and beedi tobacco are sun cured.
1.4 NICOTINE CONTENT OF TOBACCO:
Nicotine content is an important factor, which determines the quality of tobacco

from the point of view of the marketability of tobacco products since nicotine is believed
to be addictive in nature. Nicotine content is highest in beedi tobacco (6.5 % to 8.25 %).
1.5 TOBACCO WASTE SOURCES:
Tobacco waste or dust is generated at various stages of post harvest processing of

tobacco and also while manufacturing various tobacco products like cigarette and beedi.
The types of wastes generated during pre & post harvest practice of tobacco include
suckers, stems, mid ribs, leaf waste and dust. Most cigarette factories are recycling the
waste to produce reconstituted tobacco sheet and blending for the production of cheap
tobacco products.
1.6 AVAILABILITY OF TOBACCO WASTE:
Patel and Ramakrishna surveyed the tobacco wastes suitable for nicotine
extraction available in the country during 1985. According to their data an average of as
million kg of tobacco waste is available annually. According to Patel and Ramakrishna in
general 11% of total production of tobacco results in waste. The quality of tobacco waste
available if organized efforts are made to collect the waste from all economical sources
will be on an average 16% of the tobacco production as published.
The tobacco waste is also exported mainly to USA to some extend. The tobacco
dust consumed at present based on the sample data would be 25,000 tones per year for
production of 600 tones per year of nicotine content in tobacco waste.
1.7 CHEMICAL CONSTITUENTS OF TOBACCO:
Due to health and social concerns, tobacco has been the most thoroughly
researched natural products in history. Millions of dollars have been expended in the
study of tobacco constituents composition over 2700 compounds have been identified in
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various tobacco variety and it is estimated that in excess of 6000 may be in tobacco
smoke.
1.8 NICOTINE ALKALOIDS OF TOBACCO:
The species most often use for the production of tobacco because of its high level
of nicotine is N. tabacum, which is cultivated for the preparation of cigarettes, cigars and
pipe tobacco. Nicotine (C10H14 N2 ) is readily extracted from tobacco roots and stalks that
remain after the leaves have been picked for tobacco production and from waste tobacco.
It is optically pure when obtained from the tobacco plant, (pure liquid Nicotine content
varied between 2.8% to 6.5% for Beedi tobacco waste and 1.2% to 2.7% for other
tobacco wastes).
1.9 ROLE OF TOBACCO PRODUCTS IN THE ECONOMY:
Tobacco and tobacco products contributes over Rs.600 million to the export
earnings and over Rs. 30,000 million to excise revenue of the country. Tobacco sector
employees even 7.5 million people in farming curing, marketing, grading, redrying,
packing, manufacturing, exports and retail trade. India’s export of tobacco products
increase from 12,337 tones in 1981 to 18,957 tones in 1998-99 and 21,837 tones in 2006-
07. The short fall in revenue is made good by increasing rates of excise duty on
manufactured tobacco products and bringing all tobacco products under tariff structure.
The current excise revenue from tobacco products in India is esteemed at Rs. 75,000
million a year. It is because of these reasons and the difficulty in finding suitable alternate
crop to tobacco the governments are hesitance to impose total ban on tobacco use in spite
of known health risk from the use of tobacco and the related expenditure. According to a
study the cost of treating each cancer patient is Rs. 3.5 lakhs. The study has given a boost
of the campaign against tobacco, since the health cost of tobacco are much more than the
gains from its cultivation.
Tobacco made for million preventable deaths annually. In India alone 7 lakh
people die due to tobacco related diseases every year. There is a continued effort to
control the usage of tobacco globally. In the absence of suitable alternative for tobacco
crop farmers are not likely to discontinue cultivation of tobacco in spite of health risks
associated with it in such a situation alternative use for tobacco could help to control the
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supply side of tobacco for the manufacture of smoking and chewing products. Even if the
present usages of tobacco for smoking or in other forms are to continue alternate routes
of tobacco usage will help in controlling the supply side for such use. The products
developed so far include tobacco leaf proteins, tobacco seed oil, photochemical,
pharmaceutical products based on nicotine such as nicotinic acid, etc.
Increasing the cost of tobacco products has done demand side control of tobacco
usage to some extend. In country like India excise duty and sales tax compound of
tobacco products in some are as high as 60%. However, the alternate use of tobacco will
help the farmer as well as in controlling the tobacco use in the present form i.e. due to the
carcinogenic effects of tobacco can be reduced by converting nicotine to nicotinic acid
(Niacin) as per as the protection form treatment of tobacco.
1.10 RECOMMENDATIONS:
According to the global health report estimates 65% of all men use some from of
tobacco (35% smoking, 22% chewing tobacco, 8% use both). The use of smokeless
tobacco is similar among women and men. At least 1/3 of women use form of tobacco.
There are 23 major tobacco growing districts in the county. Natu tobacco is grown in Sap
districts, Hookah tobacco is grown in Bihar, WB, Gujarat and UP, chewing tobacco is
grown in TN, WB, UP and Orissa. India is the third largest consumer of tobacco next to
China (Ranks No.1) and USA.
Tobacco is rich source of protein, edible oil and various useful chemicals like
aromatic compounds, solanesol, nicotine, organic acid etc. The excise revenue from
tobacco products in India estimated at Rs.75,000 million a year. The current export
earnings from tobacco and tobacco products are about Rs.1750 million. According to
Food Administration Organisation about 7 lakh people in India die due to tobacco related
diseases per year. According to ICMR average cost of treating tobacco related cancers in
India is Rs. 3.5 lakh per case.
The need for development of alternate use for tobacco arises because of
compulsion generated mainly out of health risks of using tobacco for introducing tobacco
control laws. Tobacco is major revenue generating commodity of many countries.
Tobacco is addictive and if the use of tobacco has to be stopped it is necessary to help
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tobacco users to get rid of the habit nicotine replacement therapy needs. Nicotine
produced from tobacco for the manufacture of smoking cassation products and nicotinic
acid. Product technologies to be commercialized include nicotine extraction by Ion
exchange method, technology for other nicotine salt and nicotinic acid. Efforts should be
made to be commercialized the laboratory technology for protein extraction, tobacco seed
oil extraction. Color extraction and tobacco flavor and coenzyme and also nicotinic acid.
As a long term plan country should have its own products base for tobacco control,
nicotine and its derivatives are not used at present for the treatment of brain related
disorders research in such medical fields should be encouraged.
1.11 PROPERTIES OF TOBACCO CONTENT:-
A. Nicotine
1. It is a hazardous poison if taken in pure form.
2. It is responsible for the temporary stimulation following smoking.
3. It is the addictive property of tobacco.
4. It raises blood pressure.
5. It increases rate of heart beats.
6. It stimulates the flow of saliva.
7. It causes vasoconstriction (narrowing of the blood vessels) and lowered skin
temperature.
8. After its use it effects wear off and depresses the system.
9. Boiling point is 2470C, it is the best known and most widely distributed of the
tobacco alkaloids, it occurs naturally, when oxidized with dichromate ,H2SO4 (or
HNO3) and it forms niacin. (10)
B. Tar
1. It is a yellowish brown sticky mass of condensed particulate matter from
tobacco smoke.
2. It contains carcinogenic hydrocarbons which have tumor promoting
activity and damages the lungs.
3. It is also related to black lung diseases.
C. Carbon Monoxide
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1. It is one of the gaseous elements found in tobacco smoke.

2. It combines with the hemoglobin on the red blood cells and thereby reduces the
oxygen-carrying capacity of the blood.
Factors governing the nicotine content of tobacco are:-

1. The species, variety and strain.
2. The environment in which the plant is grown, primarily the condition of the
climate and soil.
3. Cultural, curing and handling methods employed.
The nicotine content of commercial tobacco types varies considerably, while the
ash content is high and ranges from 15 to 25% of the leaf on a water free basis.
Nicotine is used in agriculture as an insecticide and in chemistry as a source of

nicotinic acid, which is obtained by the oxidation of nicotine. Tobacco smokers absorb
small amounts of nicotine and inhales smoke and then they feel certain physiological
effects as a nerve stimulant, especially upon the autonomic nervous system promoting the
flow of adrenalin and other internal secretions. It is also believed that it can inhibit the
activity of a receptor in the brain that regulates the release the brain memory and
movement control. This can offer beneficial medical side effects and the united status it
has been used with some success in the treatment of people suffering from Parkinson’s
and Alzheimer’s deceases and children with Tourette’s syndrome.
In large doses, nicotine paralyses the autonomic nervous system by preventing the
transmission of nerve impulses across the space between cells. Still large doses of
nicotine may causes convulsions and death. The effects of nicotine upon the nervous
system vary among individuals. In some people nicotine hastens the formation of gastric
ulcers. Nicotine is now considered to be an addictive drug.
Tobacco is grown with assistance of man with the leaf as the most valuable part
of the plant. Almost all countries are capable of growing tobacco but the United States,
China, India and Brazil are the leading countries to grow tobacco. In any case it is the
nicotine content in the leaves, which attracted man to the tobacco plant. Tobacco is
primarily used for cigarette, cigar, chewing tobaccos and snuff. Other products from
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tobacco include beedi and hookah and are typically Indian products with 90% of
production coming from India.
1.12 DIESEASES FROM TOBACCO
1.12 .1 Cancers of the urinary tract
Cigarette smoke and its metabolites cause cancers of the bladder and kidney
resulting in the death of over 40 % of men in some countries of Eastern and Central
Europe, and 17 % of women in USA. Tobacco and cigarette use especially on a Western
diet (high total fat; fried or boiled meats; low in fiber, vegetables and fruits) pose a high
risk for renal cancer growth. Cigarette smoking is associated with elevated plasma
carcinoembryonic antigen (CEA) levels among patients suffering from non-neoplastic
diseases including chronic renal failure. Further studies have demonstrated that the
prominent nicotine-related alkaloid ß-nicotyrine present after smoking potentially inhibits
human CYP2A630. As CYP2A630 is involved in the metabolic activation of numerous
carcinogens reduction in this enzyme could potentially promote the development of renal
carcinoma.
1.12.2 Occupational exposure to cigarette smoke
A recent report indicates the passing of a new federal bill in Germany to reduce
exposure to environmental tobacco smoke in the workplace .Exposure to tobacco smoke
at work increases the risk of urinary detection of nicotine and cotinine two-fold. Of
concern, however, is the exposure of non-smokers to smoking family members at home.
Serum cotinine concentration by occupation has been detailed .Mean serum cotinine
levels ranged from 0.09 (farming, forestry and fishing jobs) to 0.22 ng/ml (operators,
fabricators and laborer jobs). It is interesting to note that waiters had the highest cotinine
output suggesting a high stress job. Such working conditions would presumably favour
repeated smoking and further reinforce addictive behaviors.
1.12.3 Passive smoking
Exposure to passive smoke is clearly a health risk. This includes an enhanced

exposure to carbon monoxide of a non smoking visitor in a recreational environment and
in the workplace. There is some indication of an elevated breast cancer risk associated
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with passive smoking exposure of 5 hr or more per day at work . Occupational exposure
to tobacco smoke is damaging to children .In their questionnaire study on pupils aged 13-
15 yr, smoking was found to occur at home (30.2%), at a friend’s place (29.3%), in
public places (12.1%), at social events (10.4%), and at workplaces (1.5%). Group
therapy, individual counseling, use of self-help materials, and nicotine replacement
therapy have been described. Strong evidence suggested that interventions directed at
individual smokers helped them to quit following advice from a health professional,
individual and group counseling, and pharmacological treatment.
1.12.4 Nicotine induced nephropathies
Nephropathies are accelerated by nicotine with an increased incidence of

microalbuminuria progressing to proteinuria, followed by type-1 diabetes mellitus
induced renal failure. The risk for end stage renal disease (ESRD) was independent of
age, ethnicity, income, blood pressure, diabetes mellitus, prior history of myocardial
infarction, or serum cholesterol. Smoking vastly accelerates mortality in diabetic patients.
The increased risk for macro vascular complications coronary heart disease (CHD),
stroke, and peripheral vascular disease, is most pronounced in type 2 diabetic patients.
The development of type 2 diabetes is another possible consequence of cigarette smoking
besides the better known increased risk for cardiovascular disease. Smoking is harmful to
albumin excretion because it increases the risk of microalbuminuria; shortens the interval
between onset of diabetes and the start of albuminoidal or proteinuria; accelerates the rate
of progression from microalbuminuria to persistent proteinuria; and pathologically
promotes the progression of diabetic nephropathy to ESRD.
1.12.5 Associated influence of nicotine on the nervous system
Renal injury induced by cigarette smoke condensate is reversed by renal

denervation. Cigarette smoke-induced renal damage is due, at least in part, to activation
of the sympathetic nervous system. In a study on rats exposed to long-term passive
smoking for a short period of about 24 hr after birth, the diameter of glomerulus’s in
smokers was slightly smaller than in non-smokers (96.42 ± 7.15 μm , 99.92 ± 5.56 μm
respectively).Associated elevations in nicotine-induced sympathetic nervous activity,
would justify the increase in heart rate and arterial pressure mediated by systemic
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vasoconstriction in healthy non smokers, probably through alteration of a cyclic-GMP-

dependent vasoactive mechanism. Additionally, alterations of normal sympathetic
nervous activity may contribute to volume expansion (VE) in the nephron causing a
significantly blunted diuresis and natriuresis.
1.12.6 Nicotine should be removed from combustion tobacco products
Behavioural manipulations to reduce exposure to inhalation of cigarette smoke are

important and include a switch to denicotinised cigarettes. The authors demonstrated that
switching to smoking denicotinised cigarettes for two weeks decreased the rewarding
effects of the usual-brand test cigarettes. In order to re-enforce this smoking cessation,
positive changes in behaviour through motivational counselling have been suggested.
During treatment of nicotine addiction, one study found that there is a dose-response
relationship between the number and duration of sessions and the quit rate. It was
demonstrated that smokers must select a target quit day and stop smoking completely on
that day as even a few cigarettes per day in the first fortnight resulted in relapse. The use
of nicotine replacement products or bupropion improved success rates. Alternatively
nicotine-free combustion cigarettes may help, although exposure to other combustibles
would not be prevented. (22)
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Chapter 2
LITERATURE SURVEY
2.1 DIFFERENT METHODS FOR NIACIN
2.1.1 Liquid phase oxidation of Nicotine using Chromic acid: -
The classic method of preparing nicotinic acid was by oxidizing nicotine with
potassium dichromate. This was discovered over a hundred years ago. This also serves as
an excellent example when considering green technology. Chromic acid (CrO3) is
carcinogenic and environmentally threatening. It is on the other hand is extensively used
in the tanning industry and has higher present value on the market than its precursor.
Assuming an ideal chemical reaction (100% yields) the reaction gives the following
figures:
Nicotine 1.32 tones
Chromic acid 9.02 tones
Nicotinic acid 1.00 tones
CO2 produced 1.43 tones
NOx (calculated as 0.37 tones
NO2)
Water 0.73 tones
Chromic oxide 6.8 tones
Thus almost 9 tones of side product are produced for 1 tones of desire product
Reaction:
2C10H14N2 + 22CrO3 2C6H5NO2 + 8CO2 + 2NO2 + 9H2O + 11Cr2O3
Nicotine Chronic Acid Nicotinic Acid Chronic(III) oxide
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2.1.2 Liquid phase oxidation of MEP (2-methyl-5-ethylpyridine) with nitric acid or

air: -
To avoid the problem of Picoline sourcing non-pyridine producers have used

methyl ethyl pyridine as an alternative for niacin. The liquid phase oxidation with nitric
acid is surprisingly selective and has been used since 1965 by Lonza to produce up to
15000 tones/year niacin. The reaction can be approximately represented as follow.
i)Oxidation of MEP to Nicotinic acid (Niacin):-
C8H12N + 9[O] ---------- C6H5NO2 + 2CO2 + 3H2O
2-methyl-5-ethylpyridine Nicotinic acid
ii) Oxidation of MEP with Nitric acid:-
C8H12N + 6HNO3 ------ - C6H5NO2 + 2CO2 + 6H2O + 6NO
2-methyl-5-ethylpyridine Nicotinic acid
iii) Regeneration of Nitric Acid:-
NO + [0] NO2
3NO2 + H2O 2HNO3 + NO
Methyl ethyl pyridine (MEP) is itself produced by the liquid-phase condensation

of paraldehyde and ammonia. Again this complex reaction proceeds surprisingly
selectively (>70%) and is the main reason why this material offers itself as an alternative
to the simpler molecule picoline.Continuous development and improvement of this
process over the years have led to high-quality product and to LonZa’s ability to maintain
their position as the world leader in niacin manufacture. But however many
improvements and developments have been made to this process, it intrinsically holds
some disadvantages, when considered from the ‘green’ stand point.
2.1.3 Liquid-Phase oxidation of 3-Picoline with Oxygen: -
Picoline can be selectively oxidized with air in the liquid phase to niacin. A
catalyst combination such as cobalt and manganese acetate or bromide is usually used in
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an acetic acid medium and the air-oxidation takes place under elevated temperatures and
pressures.
2.1.4 Gas phase oxidation of Picoline to Nicotinic acid: -
Employing the cyanopyridine route for the production of nicotinic acid involves
the fixation of a nitrogen atom in the ammoxidation step, followed by its removal in the
ultimate hydrolysis. This is a contradiction to the principles of a green process and in the
last ten years, efforts have been made to oxidize Picoline in the gas phase directly to
nicotinic acid. It is this process that in terms of green chemistry represents the state of the
art today.
2.1.5 Gas- Phase oxidation of Picoline to Cyanopyridine:-
The gas phase ammoxidation to cyanopyridine followed by a hydrolysis

either to nicotinamide or nicotinic acid are commercial processes and for the production
of nicotinamide, represents the most logical and direct route via 3-picoline.
2.1.6 Commercial method followed by “Amsal Chemical Pvt. Ltd. Ankaleshwar:-
98% H2SO4 is taken in stainless steel batch reactor, in which 90% β-picoline was
charged slowly to maintain the temp of the reactor 40-500C. Due to exothermic reaction,
the vessel is cooled externally by cold water in jacket and reactor is stirred continuously
for time span of 30-40hrs. When charging of β-picoline is completed the mass in vessel is
heated up to 800C, β-picoline sulphate is formed. The reaction mass is charged in the
second reactor which is glass line reactor for oxidation with 60% HNO3. The temp of the
vessel is maintained at 180-1900C. Nicotinic acid sulphate forms along with NO and
water, then precipitations was carried out with NH3 to get niacin.
Reaction:
Sulphonation
1. C6H7N + H2SO4 C6H11SO4
B-Picoline β - Picoline Sulphate
Oxidation
2. C6H11SO4 + 2HNO3 C6O6H9SN + (No)x + H2O
β -Picoloine Sulphate Nicotinic Acid Sulphate
Precipitation
3. C6O6H9SN + 2NH3 C6O2H5N + (NH4)2SO4
Nicotinic Acid Sulphate Niacin Ammonium Sulphate
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2.1.7 Finally, Niacin may be synthesized from pyridine:-
Bubbling CO 2 into a solution of pyridine and LiAlH4 in dioxane gives an 80-90%

yield of nicotinic acid. (3)
2.2 REVIEW ARTICLE (20)
2.2.1 Effect of tobacco smoking on renal function:-
Nicotine is one of many substances that may be acquired through active and
passive smoking of tobacco. In man, nicotine is commonly consumed via smoking
cigarettes, cigars or pipes. The addictive liability and pharmacological effects of smoking
are primarily mediated by the major tobacco alkaloid nicotine. High stress jobs favour
repeated smoking and further reinforce addictive behaviors. There are elevated serum
cadmium and lead levels in smokers resulting in glomerular dysfunction. Nephropathies
are accelerated by nicotine with an increased incidence of microalbuminuria progressing
to proteinuria, followed by type-1 diabetes mellitus induced renal failure. Cigarette
smoke-induced renal damage is due, at least in part, to activation of the sympathetic
nervous system resulting in an elevation in blood pressure. Ethanol, nicotine, or
concurrent intake significantly increases lipid peroxidation in liver, and decreased
superoxide dismutase activity and increased catalase activity in the kidney. This review
describes the effects of nicotine, smoking, smoke extracts and other tobacco constituents
on renal and cardiovascular functions, and associated effects on the nervous system. Both
active and passive smoking is toxic to renal function.
2.2.2 Past work:
Past work was carried out By Prof. B.V.Babu et. al. They conclude that pure
tributyl phosphate (TBP) and the combination of TBP and diluents gave a higher
distribution coefficient as compared to pure solvent the polar diluents may be more
effective with phosphorus – bonded oxygen bearing extractants distribution coefficients
for extraction of nicotinic acid using TBP was higher than pure solvents.
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2.2.3 Indian J Med Res 124, September 2006, pp 261-268
There are numerous harmful substances found in tobacco and tobacco smoke.
Nicotine is one of these substances that may be acquired through active and passive
smoking. Associated with nicotine exposure is the incidence of occupational influences,
passive smoking, nephrotoxicity, induced nephropathy and possible treatments. This
review aims to describe the influence of nicotine, smoking, smoke extracts and tobacco
contaminants on renal function, with associated effects on cardiovascular function and
various signal transduction pathways, by incorporating current references and
expounding on previous reviews. A discussion and recommendation for denicotinising
cigarettes and tobacco products are also presented.
2.3 NON-ADDICTIVE TOBACCO PRODUCTS (24)
Cut tobacco used for processing cigarettes or other smoking articles is reacted
with an agent such as an oxidant or subject to an extraction/removal process for a suitable
period of time, dependent upon the nicotine content, the oxidant employed and the
reaction temperature or extraction condition, or distillation, such that the nicotine
embedded in the leaf is then converted into nicotinic acid or niacin. Sufficient conversion
or extraction or distilled is allowed to occur so that either no nicotine or only a minimal
amount of free nicotine remains in the smoking article. Upon intake into the lungs and
hence the blood stream of the smoker or other tobacco user, will result in a blood plasma
content of nicotine ranging from 0 to less than about 5 nanograms per milliliter of blood
plasma. This effectively insures that the addictive process in smoking or other tobacco
intake cannot be initiated or maintained. Nicotinic acid or niacin is not an addictive
component of the tobacco. The niacin thus formed is located in the interstices or on the
surface of the tobacco and when inhaled, actually serves as a beneficial nutrient, such as a
vitamin. Flavorants can be added for taste and other non-addictive stimulants can be used
to produce a heightened sense of awareness or well being.
2.3.1. Field of the Invention
This invention relates in general to certain new and useful improvements in

processing of tobacco to eliminate or convert nicotine in the tobacco into nicotinic acid as
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a harmless or beneficial product such that the nicotine level which can be achieved by use
of the tobacco product results in a blood plasma level consonant with non-addiction.
2.3.2. Brief Description of the Related Art
The effect of nicotine in tobacco on the central nervous system primarily is

located in the locus ceruleus, which produces increased mental activity, as well as in the
mesolimbic center, which stimulates the desire for more nicotine, giving rise to nicotine
addiction. The basic cause of addiction lies in the inhalation of small amounts of nicotine
and the circulation in the blood of amounts of nicotine in the order of twenty to twenty-
five nanograms per milliliter. Conventional cigarettes contain a varying range of nicotine
content which may vary, for example, from about 0.2% to about 5%.
It is also well known that the smoking of tobacco products generates other
deleterious components, such as tars, and upon combustion, carbon monoxide. It is also
well established, (New Scientist, 1938, Aug. 13, 1994 v. 143, page 10) that about one to
three milligrams of nicotine will be absorbed in the lungs during each smoking interval.
Information exists on the proof of the addictive properties of nicotine in the
aforementioned New Scientist article.
There is a wealth of literature relevant to the elimination of deleterious

substances, such as the nicotine and tar from tobacco products. U.S. Pat. No. 5,240,014
teaches of the catalytic conversion of carbon monoxide. U.S. Pat. No. 5,158,099 teaches
of a wetted impact barrier for reduction of tar and nicotine. U.S. Pat. No. 4,700,723
teaches of a filter consisting of a fibrous ion exchange resin which removes ionic and
carcinogenic constituents, as well as nicotine and tar from the tobacco smoke. U.S. Pat.
No. 4,250,901 describes a chemical denaturant, such as water, to eliminate or trap
nicotine, tar and carbon monoxide. However, each of these approaches are highly
impractical. As an example, nicotine reacted with peroxide results in n-methylpyrolle
pyridine and nicotinic acid and in which the n-methylpyrolle pyridine is far less than a
healthful addition to a tobacco product.
The prior art also teaches of the extraction of nicotine from a raw tobacco product
by steaming procedures. For example, in German Patent No. 25,403 by Dr. Johannes
Sartig using super heated steam. In like matter, and in related techniques, U.S. Pat. Nos.
18
2,525,784 and 525,785 teach of the use aluminum sulfate and ammonia-ethylene
dichloride to separate nicotine from raw tobacco product.
In addition to the foregoing, various nicotine blood plasma antagonists have also
been suggested for use in eliminating nicotine addiction. However, these antagonists,
such as mecamylamine, have only proved partially successful, if at all. One practical
solution, however, to the nicotine addiction problem is suggested in this application
namely a chemical conversion of the nicotine in tobacco to obviate its effect on the
acetylcholine brain receptor. The alternative use of antagonists however only lends itself
to expensive long term basic research and with vanishingly small chances of success.
There is other patent literature available which has tangential relationship to the
use of modified tobacco products or agents related to the use of tobacco products. U.S.
Pat. No. 5,122,366 teaches of the incorporation of silver nitrate in mouthwash to reduce
nicotine taste from the mouth after smoking and ingestion of nicotine into the lungs.
However, this is obviously no impediment to an addictive process. U.S. Pat. No.
4,620,554 uses a composition for enhancing the taste of cigarettes and which includes a
filter containing ascorbic acid, powdered vegetable oil and fats, comfrey leaves, wheat
protein, beef stock plant and a flavorant, such as a Japanese mint and vanilla. The effect
of the composite is to produce a mellow taste and less irritation. Nicotine and the tar are
absorbed by the oils and the fats and the ascorbic acid and its isomers decrease the
nicotine, tar and carbon monoxide which is drawn into the lungs of the user. Potassium
nitrate is also incorporated in the filter and improves combustion and catalyzes nicotine
to nicotinic reaction.
U.S. Pat. No. 3,943,940 teaches of the contacting of potassium permanganate to

oxidize nicotine just before smoking. However, this technique is quite awkward and
expensive and not amenable to widespread public acceptance. More importantly, the
results have been found to be quite variable and have no relationship to the amount of
nicotine ingested by the individual.
Not with standing the foregoing, none of the proposed approaches for modifying
tobacco have recognized any relationship between the amount of nicotine present and the
amount absorbed in the blood stream of the user compared to the addictive effects
19
thereof. Nevertheless, the importance of nicotine in the addictive process is indicated in

the Wall Street Journal of Oct. 18, 1995, where it was acknowledged that diammonium
phosphate (DAP) increases nicotine delivery in reduced nicotine and tar cigarettes.
2.4 OBJECTS
1) It is, therefore, one of the primary objects of the present invention to

provide a tobacco product adapted for human use and which eliminates an
addictive response to the user.
2) It is another object of the present invention to provide an improved

tobacco product of the type stated which utilizes an oxidized tobacco in which
nicotine has been converted to nicotinic acid or extraction to a level such that
when used, the blood plasma nicotine level resulting in the user is about 0 to
about 5 nanograms per milliliter.
3) It is a further object of the present invention to provide an improved

tobacco product of the type stated in which a tobacco product is converted
chemically or by physical means to obviate any effects on the acetylcholine
brain receptors in an individual smoking or otherwise ingesting such tobacco
product.
4) It is an additional object of the present invention to provide an improved

tobacco product of the type stated which can be produced at a relatively low
cost and which is highly effective in eliminating any addictive response.
5) It is another salient object of the present invention to provide a method for

altering a tobacco product in order to reduce the nicotine content therein to a
level where the resulting nicotine blood plasma level of the user has a range of
about 0 to 5 nanograms per milliliter of blood.
With the above and other objects in view, the invention resides in the novel
features of the modified tobacco product and the process for the same as hereinafter
described and pointed out in the claims.
20
2.5 SUMMARY OF THE INVENTION
In accordance with the present invention, it has been found that by converting the
nicotine of a tobacco product into a harmless and actually beneficial substance, such as
nicotinic acid, addiction to the tobacco product can be avoided. Conversion allows for a
tobacco product relatively free of nicotine and when taken into the lungs does not result
in or sustain addiction. The addictive nature of the nicotine is eliminated when the
resultant amount of the nicotine in the blood plasma of a user has a level of about 0 to
about 5.0 nanograms of nicotine per milliliter of blood.
Nicotine intake in women was measured by the presence of cotinine, which is an

oxidative metabolite of nicotine, and was detected in 84% of the female smokers and
found in the cervical mucous. See J. Cancer Epidemiol, Biomarkers Prev. 1992 (1)(2)
125-9. In numerous other citations in the literature, there is described a movement of
nicotine into the blood plasma and then into vital organs. Indeed, the impact of nicotine
on heart and pulmonary system and the resultant formulation of neoplastic conditions in
the body are well known and acknowledged in the art.
The important aspect of the present invention is the actual finding that nicotine
addiction can be reduced and completely eliminated by use of smoking devices such as
cigarettes in which the nicotine content is sufficiently small so that when introduced into
the blood stream of a user, it will not cause a nicotine level exceeding 0 to about 5
nanograms per milliliter of blood plasma. This can be easily accomplished by
conventional oxidation techniques or steamed installation/extraction techniques known in
the prior art for removal of nicotine. It can also be more readily accomplished by the
oxidation of the nicotine.
The key to the use of an economical treatment of a tobacco leaf or processed

tobacco are those chemical agents capable of converting nicotine into a neutral or
beneficial compound which does not require removal from the tobacco or any
surrounding matrix. Moreover, use of preferred chemical or oxidizing agents render the
content of tar in the tobacco less noxious or otherwise, more solubilized if extraction of
the tars is required.
21
In accordance with the present invention, there is provided an improved tobacco

product adapted for human use and which eliminates an addictive response in the user.
The improved tobacco product has been oxidized under conditions in which the nicotine
contained in the product has been converted to nicotinic acid to a level such that the
resulting nicotine concentration in the blood plasma of the user has a level of 0 to about 5
nanograms of nicotine per milliliter of blood. As indicated previously, it has been found
in accordance with the present invention that when the nicotine level is reduced to about
5 nanograms per milliliter or less, there is no addictive response in the user. This is an
important factor in that it has now been realized that one can actually continue to use a
tobacco product without at least suffering the addictive effects which otherwise arise
based on prolonged use of tobacco products.
In a more preferred embodiment of the invention, the nicotine in the tobacco

product is converted to nicotinic acid by means of an oxidizing agent, such as nitric acid.
Otherwise, the oxidizing agent for converting the nicotine to nicotinic acid can be
selected from the class consisting of catalyzed sulfuric acid, alkaline potassium
permanganate, hydrogen peroxide, ozone and combinations thereof, as well as other
known oxidizing agents for this purpose.
While the literature has discussed the use of oxidizing agents for oxidizing the
nicotine contained in the tobacco to nicotinic acid, no one has recognized that reducing
the nicotine concentration to a level of approximately 5 nanograms of nicotine per
milliliter of blood or less will eliminate the harmful addictive effects of the nicotine.
In accordance with the present invention, it is also possible to incorporate a

flavoring agent in the resultant oxidized product. Further, it is also possible to incorporate
in the tobacco a stimulatory agent which is non-addictive. For example, caffeine is a
highly effective stimulatory agent and while it has habit forming effects, it has been
generally recognized that those effects are not harmful.
The present invention also provides an improved process for enabling the use of
tobacco products for human intake without any addictive response arising out of the use
thereof. Again, this process comprises the converting of the nicotine contained in the
tobacco product to nicotinic acid such that there is no nicotine or only a relatively small
22
amount of nicotine remaining in the tobacco product. The process further allows the use
of the converted tobacco product so that the resultant nicotine concentration in the blood
stream of the user, when the tobacco product is used, is zero or less than about 5
nanograms of nicotine per milliliter of blood. As indicated, this eliminates an addictive
response to the use of the tobacco product.
The complexity of nicotine addiction likely will result in a bifurcated approach in

which the use of nicotine converted tobacco will be emphasized for pre-addictive
individuals, such as the pre-addictive teenager, as opposed to the experienced smoker,
already well addicted and experiencing nicotine blood level steady state concentrations
from about twenty to twenty-five nanograms per milliliter or higher.
It may be that the long term strongly addicted smoker may not only require the
physiological impact of this invention but that additional or concurrent auxiliary
treatment may be required due to ingrained motivational factors.
This invention possesses many other advantages and has other purposes which
will be made more clearly apparent from a consideration of the forms in which it may be
embodied. Some of these forms will be described in detail in the following detailed
description which is set forth merely for purposes of illustrating the general principles of
the invention. However, it is to be understood that this detailed description is not to be
taken in a limiting sense.
There is also a large amount of patent literature relating to the above reactions,
although all of the literature to date does not reflect the very essence of this present
invention which is the reduction of substantially all of the nicotine and conversion to
nicotinic acid which thereby results in an nicotine concentration in the blood stream of
the tobacco user in an amount of about 5 nanograms per milliliter of blood or less. This
level has been found to eliminate tobacco product addiction in the user.
In accordance with the present invention, it has been found that the user of
a tobacco product can still continue to use the tobacco product for the other sensory
effects which are provided without being addicted. Thus, the conversion of the nicotine in
accordance with the present invention not only eliminates the addiction, but also reduces
some of the harmful effects of the tars. In this way, a party may continue to use tobacco
23
products without the attendant fear of becoming addicted. This is particularly effective
for those parties who wish to experiment or use tobacco and who have not yet become
seriously addicted to the tobacco product. Even upon smoking or other use of the product,
some niacin particulates may be ingested or inhaled. This is not detrimental and indeed
may be beneficial to the user. Upon inhalation of tobacco smoke or other use of the
tobacco treated according to the present invention, blood levels of nicotine will not rise
above 5 nanograms per milliliter of blood and will preferably approach 0 nanograms per
milliliter of blood plasma. (24)
24
Chapter 3
CONVERSION OF NICOTINE TO NICOTINIC ACID

3.1 NICOTINE - SOURCES AND HEALTH ASPECTS:-
3.1.1 Sources
Animal products: Fruits and Seeds: Fungi:

vegetables:
• liver, heart • leaf • nuts • mushrooms
and kidney vegetables • whole grain • brewer's yeast
• chicken • broccoli products
• beef • tomatoes • legumes
• fish: tuna, • carrots • saltbush
salmon • tobacco seeds
• milk leaves
• eggs • sweet
potatoes
• asparagus
• avocados
The tobacco plant contains over 2,200 compounds of which nitrogenous
compounds.Comprise more than 30 percent. Torikai et al demonstrated that in burley
tobacco leaves; there is a significantly higher content of pyridinic nitrogen than in bright
or oriental tobacco leaves. The profiles of 29 known toxic compounds in tobacco smoke
have been mentioned. Nicotine C10H14N2; Mol.wt = 162.23 is one important alkaloid
contained in tobacco leaves. Nicotine, however, is not the principle adverse constituent in
combustion cigarette products. The primary commercial source of nicotine is by
extraction from the dried leaves of the tobacco plant (Nicotinia tabacum). Smoking may
affect people of any age, nicotine traveling rapidly in the blood stream and carbon
monoxide binding to haemoglobin in red blood cells. In addition, the carcinogen benzo
pyrene binds to cells in the airways and major organs of smokers, and depresses immune
function. Smoking results in an elevated incidence of chronic inflammation as a
25
consequence of oxidative stress. Cigarette smoking increases the risk of developing

numerous cancers including the lip, mouth, pharynx, oesophagus, pancreas, larynx, lungs,
uterine cervix, urinary bladder and kidneys. Cigarette smokers are 2-4 times more likely
to develop coronary heart disease than non-smokers. Contact with second hand or passive
smoke exposes people to approximately 50 carcinogens resulting in an elevated risk of
lung cancer and coronary heart disease, and an increased incidence of asthma, bronchitis
and pneumonia in children.
450 gms. (One pound) of smoke curved burley tobacco is treated with 9.50 lit (2.5
gallons) of an oxidizing agent having 50% of HNO3 for about 30 min at a temp of about
1100C to 1150C. The burley tobacco was introduced into a glass container and the HNO3
was poured directly onto the tobacco and the tobacco was allowed to remain in the
oxidizing bath in this container for the 30 min period at 1100C temp. After 30 min. the
treated tobacco was rinsed with tap water and dried in a tray dryer and with filter paper.
(24)
Nicotine may be recognized by the addition of a drop of 30 % formaldehyde, the

mixture being allowed to stand for one hour and the solid residue then moistened by
a drop of concentrated H2SO4 , when an intense rose red colour is produced.
It was found that the HNO3 contacts with tobacco (Nicotine) for sufficient time
(30min) convert all of the nicotine to nicotinic acid.(24)
3.1.2 Main Reaction:
C10H14N2 + 9[O] --HNO3--- C6H5NO2 + C2H2O4.H2O + CH3NH2 + CO2
Nicotine Nascent Oxygen Nicotinic acid Oxalic Acid Methylamine
With the help of this treatment to tobacco the addictive nature of man towards
tobacco becomes non-addictive. Also it provide an improved tobacco product of the type
which utilizes an oxidized tobacco in which nicotine has been converted to nicotinic acid
or extraction to a level such that when used the blood plasma nicotine level resulting
about 0 to 5 nanograms / ml. With the above objective in view, the different unit
operations and process are carried out to covert maximum amount of nicotine to nicotinic
acid and it is extracted and analysis of product is done. Generally beedi tobacco contains
26
2 to 8 % nicotine. Dry tobacco leaves contain about 5% nicotine combined with citric or
malic acid.
3.2 PHYSICAL PROPERTIES (11)

Sr
Form &
. Name Formula Mol.wt Sp.gravity M.P.0C B.P.0C Solubility in 100 parts
colour
No
H2O Alcohol Ether
Oily
1. Nicotine C10 H14N2 162 Colourless 1.009 < 80 246 Soluble ---- ----
Liquid
Nicotinic acid Colourless Soluble Soluble Very slight
2. C6H5 NO2 123 1.473 236 Subl
(Niacin) powder hot hot soluble
Colourless 0.699 X Very Very
3. Methyl amine CH3 NH2 31 -92.5 -6.7 ------
gas 10-11 soluble soluble
HO2C Colourless
4. Oxalic acid 126 1.653 101.5 Subl Soluble Soluble 1.3
CO2H3O monoclinic
Soluble acid
Carbon Colourless Subl. 179.7 90.1 alkali
5. CO2 44 1.53 -56.6
dioxide gas –78.5 CC CC (aq.NaoH or
KOH)
Colourless
6. Nitric acid HNO3 63 1.502 ---- ----- ------ ----- ---
Liquid
3.3 PROCESS DESCRIPTION:-
The waste tobacco from tobacco processing industries and tobacco farms was
collected and dried in sun light to crush for 40 mesh size. Crushing is done in Pulverizer.
The crushed tobacco was feed in to mixing tank. In mixing tank it is mixed with water at
60 0 C to get tobacco extract. This tobacco extract was filtered, the filtrate was used for
further processing and the wet tobacco after drying can be used as non addictive tobacco
product.
The filtrate from filter press was send to mixing tank. In mixing tank little amount
of NaOH is added to maintain pH in the range 8.0 to 9.5. This mixture from storage tank
was send to Steam Distillation. In Steam distillation initially the steam is fed with feed
27
mixture and then it is feed to the jacket. From the top of steam distillation the vapours are
send to condenser & waste can be withdrawn from bottom, which can be used as fertilizer
for farming purpose. The condensed Nicotine solution was stored in separator at room
temperature.After half an hour the oily top Nicotine layer was send to Oxidation reactor
& other constituents are withdrawn from bottom of separating tank.
In oxidation reactor the main oxidation reaction occurs at 1100C and after 30 min.
time span. 50 % HNO3 was used as oxidant. The nascent oxygen according to reaction
reacts with Nicotine and it forms Nicotinic acid, methylamine, oxalic acid and carbon
dioxide. These products are stored in accumulator at room temperature. After half an
hour there was formation of two layers. The top layer is of nicotinic acid and the bottom
layer is of oxalic acid. The wet nicotinic acid was dried in a tray dryer with hot air and
finally we get nicotinic acid powder.
The confirmation of Nicotinic Acid was done as, 100 mg of dried powder was
mixed with 10 mg of citric acid, 3 drops of acetic anhydride and heat on a water-
bath, the mixture attains red-violet color. (5)
3.2.1 Nicotine consumption
In man, nicotine is commonly consumed via smoking cigarettes, cigars or pipes.

Nicotine may also enter the body via low tar Eclipse cigarettes, snuff, tobacco chewing,
and pharmaceutical nicotine products like nicotine patches. Smokeless tobacco contains
28 carcinogenic agents and increases the risk of developing cancer in the mouth, as well
as leading to nicotine addiction and dependence. The cigarette has been described as an
efficient nicotine carriage device delivering an optimum dose of nicotine to the dependent
brain. Ventilated cigarette filters dilute smoke with air and reduce standard yields of tar,
nicotine and carbon monoxide. There is, however, no convincing evidence that changes
in cigarette design have significantly reduced diseases caused by cigarettes. Nicotine
replacement therapy can occur through products like the Niquitin CQ transdermal patch;
the Nicorette Microtab; the Nicorette inhalator; and the Nicotinell lozenge. These
alternatives are safer than exposure to combusted tobacco which has numerous other
constituents that are harmful to the body. Indeed, the risk of nicotine replacement therapy
is very low. Other therapies promoting an increased smoking cessation rate with little
28
effect on withdrawal symptoms, for example, nortriptyline (started at 25 mg 14 days

before quit day, titrated to 75 mg/day as tolerated) combined with transdermal nicotine
(21 mg/day) may represent an option for smokers in whom standard therapy has failed
3.2.2 Nicotine addiction and metabolism
Nicotine has a dangerous effect on the body by modulating behaviour and

dependence resulting in addiction and subsequent repeated exposure to toxins found in
tobacco and tobacco smoke. Social aspects, peer pressure, stress, alcohol consumption,
etc., are all behavioural factors that contribute towards addiction. The addictive liability
and pharmacological effects of smoking are primarily mediated by the major tobacco
alkaloid nicotine. Nicotine is metabolized to S- (-)-nicotine D1'–5'-iminium ion by the
genetically variable hepatic enzyme cytochrome P-450 2A6 (CYP2A6) and then to the
pharmacologically less active derivative, S-cotinine (cotinine), by aldehyde oxidase.
"A hundred pounds of the dry tobacco-leaf yield about seven pounds of nicotine.
One drop applied to the tongue of a cat brought on convulsions, and in two minutes
occasioned, death. The Hottentots are said to kill snakes by putting a drop of it on their
tongues. Under its influence, the reptiles die as instantaneously as if killed by an electric
shock," says John Lizars, M.D., The Use and Abuse of Tobacco (Edinburgh: 1856, 1857,
1859, reprinted, Philadelphia: P. Blakiston, Son & Co, 1883), p 57.
29
Chapter 4
NIACIN
4.1 HISTORY
Niacin was first described by Weidel in 1873 in his studies of nicotine. The
original preparation remains useful: the oxidation of nicotine using nitric acid. Niacin
was extracted from livers by Conrad Elvehjem who later identified the active ingredient,
then referred to as the "pellagra-preventing factor" and the "anti-blacktongue factor."
When the biological significance of nicotinic acid was realized, it was thought
appropriate to choose a name to dissociate it from nicotine, in order to avoid the
perception that vitamins or niacin-rich food contains nicotine. The resulting name 'niacin'
was derived from nicotinic acid + vitamin. Niacin is referred to as Vitamin B 3 because
it was the third of the B vitamins to be discovered. It has historically been referred to as
"vitamin PP."
4.2 DIETARY NEEDS
Severe deficiency of niacin in the diet causes the disease pellagra, where as mild
deficiency slows the metabolism, causing decreased tolerance to cold. Dietary niacin
deficiency tends to occur only in areas where people eat corn (maize), the only grain low
in niacin, as a staple food, and that do not use lime during meal/flour production. Alkali
lime releases the tryptophan from the corn in a process called nixtamalization so that it
can be absorbed in the intestine, and converted to niacin. The recommended daily
allowance of niacin is 2-12 mg/day for children, 14 mg/day for women, 16 mg/day for
men and 18 mg/day for pregnant or breast-feeding women.
4.3 PROPERTIES:
1. Anti pellagra vitamin.
2. Colorless or white crystalline powder.
3. Soluble in water and boiling alcohol.
4. Insoluble in most lipid solvent.
5. No hygroscopic and stable in air.
6. It is resistant to heat, oxidation and alkalis.
30
7. It is in fact, one of the most stable vitamins.
4.3 PHARMACOLOGICAL USES:-
Niacin, when taken in large doses, blocks the breakdown of fats in adipose tissue,
thus altering blood lipid levels. Niacin is used in the treatment of hyperlipidemia because
it reduces very-low-density lipoprotein (VLDL), a precursor of low-density lipoprotein
(LDL) or "bad" cholesterol. Because niacin blocks breakdown of fats, it causes a decrease
in free fatty acids in the blood and, as a consequence, decreased secretion of VLDL and
cholesterol by the liver. By lowering VLDL levels, niacin also increases the level of high-
density lipoprotein (HDL) or "good" cholesterol in blood, and therefore it is sometimes
prescribed for patients with low HDL, who are also at high risk of a heart attack. Niacin
is sometimes consumed in large quantities by people who wish to fool drug screening
tests, particularly for lipid soluble drugs such as marijuana. It is believed to "promote
metabolism" of the drug and cause it to be "flushed out." Scientific studies have shown it
does not affect drug screenings, but can pose a risk of overdose, causing arrhythmias,
metabolic acidosis, hyperglycemia, and other serious problems.
4.4 TOXICITY
People taking pharmacological doses of niacin (1.5 - 6 g per day) often experience
a syndrome of side-effects that can include one or more of the following:
 Dermatological complaints.
 Facial flushing and itching.
 Dry skin.
 Skin rashes including acanthosis nigricans .
 Gastrointestinal complaints.
 Dyspepsia (indigestion).
 Liver toxicity.
 Fulminant hepatic failure.
 Hyperglycemia.
 Cardiac arrhythmias.
 Birth defects.
31
Facial flushing is the most commonly-reported side-effect. It lasts for about 15 to

30 minutes, and is sometimes accompanied by a prickly or itching sensation, particularly
in areas covered by clothing. This effect is mediated by prostaglandin and can be blocked
by taking 300 mg of aspirin half an hour before taking niacin, or by taking one tablet of
ibuprofen per day. Taking the niacin with meals also helps reduce this side-effect. After 1
to 2 weeks of a stable dose, most patients no longer flush. Slow or "sustained"-release
forms of niacin have been developed to lessen these side-effects .One study showed the
incidence of flushing was significantly lower with a sustained release formulation though
doses above 2 g per day have been associated with liver damage, particularly with slow-
release formulations. High-dose niacin may also elevate blood sugar, thereby worsening
diabetes mellitus. Hyperuricemia is another side-effect of taking high-dose niacin, and
may exacerbate gout. Niacin at doses used in lowering cholesterol has been associated
with birth defects in laboratory animals, with possible consequences for infant
development in pregnant women. Niacin at extremely high doses can have life-
threatening acute toxic reactions. Extremely high doses of niacin can also cause niacin
maculopathy, a thickening of the macula and retina which leads to blurred vision and
blindness.
4.5 BIOSYNTHESIS
Biosynthesis: Tryptophan → Kynurenine → Niacin
The liver can synthesize niacin from the essential amino acid tryptophan,
requiring 60 mg of tryptophan to make one mg of niacin. The 5-membered aromatic
heterocycle of tryptophan is cleaved and rearranged with the alpha amino group of
tryptophan into the 6-membered aromatic heterocycle of niacin.
Vitamin B3 is made up of niacin (nicotinic acid) and its amide, niacinamide, and
can be found in many foods, including yeast, meat, fish, milk, eggs, green vegetables, and
cereal grains. Dietary tryptophan is also converted to niacin in the body. Vitamin B 3 is
32
often found in combination with other B vitamins including thiamine, riboflavin,

pantothenic acid, pyridoxine, cyanocobalamin, and folic acid.
4.6 PHYSICAL PROPERTIES OF NICOTINIC ACID (11)

Property Value
Molecular weight 123.11
Melting point 2360 C
Sublimation range >1500 C
Density of Crystals 1.473 gm/cm3
True dissociation constants in water at 250C
Ka 1.5X10-5
Kb 1.04X10-12
pH of saturated aqueous solution 2.7
Solubility of Niacin in Water
At 00 C 8.6 gm/lit.
At 380 C 24.7 gm/lit.
At 1000C 97.6 gm/lit.
Solubility of Niacin in Ethanol,96 %
At 00 C 5.7 gm/lit.
At 780 C 76.0 gm/lit.
Solubility of Niacin in Methanol
At 00 C 63.0 gm/lit.
At 620C 345.0 gm/lit.
Basically, the coenzymes of niacin help break down and utilize proteins, fats, and
carbohydrates. Vitamin B3 also stimulates circulation, reduces cholesterol levels in the
blood of some people, and is important to healthy activity of the nervous system and
normal brain function. Niacin supports the health of skin, tongue, and digestive tract
tissues. Also, this important vitamin is needed for the synthesis of the sex hormones, such
as estrogen, progesterone, and testosterone, as well as other corticosteroids.
Niacin, taken orally as nicotinic acid, can produce redness, warmth, and itching
over areas of the skin; this "niacin flush" usually occurs when doses of 50 mg. or more
are taken and is a result of the release of histamine by the cells, which causes
vasodilation. This reaction is harmless; it may even be helpful by enhancing blood flow
to the "Flushed" areas, and it lasts only 10-20 minutes. When these larger doses of niacin
are taken regularly, this reaction no longer occurs because stores of histamine are
reduced. Many people feel benefit from this "flush," but if it is not enjoyable,
supplements that contain vitamin B3 in the form of niacinamide or nicotinamide can be
33
used, as they will not produce this reaction. (Note: When vitamin B3 is used to lower
cholesterol levels, the nicotinic acid form must be used; the niacinamide form does not
work for this purpose.)
Niacin is used to support a variety of metabolic functions and to treat a number of

conditions. Many niacin deficiency symptoms can be treated by adjusting the diet and by
supplementing B3 tablets along with other B complex vitamins. Many uses of niacin are
based primarily on positive clinical experience and are not as well supported by medical
research, although more studies are being done. Niacin helps increase energy through
improving food utilization and has been used beneficially for treating fatigue, irritability,
and digestive disorders, such as diarrhea, constipation, and indigestion. It may also
stimulate extra hydrochloric acid production. Niacin, mainly as nicotinic acid, helps in
the regulation of blood sugar (as part of glucose tolerance factor) in people with
hypoglycemia problems and gives all of us a greater ability to handle stress. It is helpful
in treating anxiety and possibly depression. B3 has been used for various skin reactions
and acne, as well as for problems of the teeth and gums. Niacin has many other common
uses. It is sometimes helpful in the treatment of migraine-type headaches or arthritis,
probably in both cases through stimulation of blood flow in the capillaries. This vitamin
has also been used to stimulate the sex drive and enhance sexual experience, to help
detoxify the body, and to protect it from certain toxins and pollutants. For most of these
problems and the cardiovascular-related ones mentioned below, the preference is to take
the "flushing" form of niacin, or nicotinic acid, not niacinamide.
34
4.7 FUNCTIONS OF VITAMIN B3 NIACIN:-
Niacin is important for proper blood circulation and the healthy functioning of the
nervous system.
It maintains the normal functions of the gastro-intestinal tract and is essential for the
proper metabolism of proteins and carbohydrates.
It helps to maintain a healthy skin.
Niacin dilates the blood vessels and increases the flow of blood to the peripheral capillary
system.
This vitamin is also essential for synthesis of the sex hormones, namely, oestrogen,
progesterone, and testosterone, as well as cortisone, thyroxin, and insulin.
4.8 CHEMICAL STRUCTURE (25)
Nicotinic Acid is water soluble. This is quite important because it may be lost
when we cook our food by boiling it in water! It is also important because it cannot be
stored in the body and must therefore be present in our diet to replace that which is lost in
urine. It is more important for us to understand why a deficiency of this chemical causes
pellagra.
Nicotinamide can
be used instead of nicotinic
acid. As we can see from these two structural formulae they are almost the same.
4.9 BIOLOGICAL SYNTHESIS
35
Humans do not have the ability to synthesise sufficient nicotinic acid, this means
that it is an essential component of a balanced diet. Some mammals are able to synthesise
this chemical so it is not an essential component of their diets. For example, dogs can
synthesise nicotinic acid from the amino-acid tryptophan. This might be an essential
amino-acid, but for dogs, nicotinic acid is definitely NOT a vitamin. Bacteria in our large
intestines, the colon, may convert tryptophan into nicotinic acid; this means that we could
survive if sufficient bacterial activity took place. Our intestinal bacteria would require 60
mg of tryptophan to synthesise 1 mg of nicotinic acid so don't count on them.
4.10 SOURCES
Nicotinic Acid is found in milk, yeast, eggs, etc. Here is a table of average values
for the Nicotinic Acid content of a variety of foods.
Food Content mg/100gg/10gm
Meat Extract 60.0
Marmite 58.5
Roast Beef 5.0
Sardines in Oil 5.0
Kippers 4.2
Whole meal Bread 3.5
Beer 0.7
Boiled Cabbage 0.15
Milk 0.08
Pellagra is associated with a low standard of living. It is particularly prevalent; in

areas where maize forms the staple diet. Maize has a very low content of nicotinic acid;
furthermore, the proteins in maize are deficient in tryptophan.
36
4.11 SOURCE CATEGORIES:

 Richest Sources: Yeast, Rice polishing, & Tobacco.
 Good sources: Meat, Liver & Poultry.
 Fair sources: Milk, Eggs, Tomatoes, Leafy green vegetables.
 Poor sources: Most Fruits & Vegetables.
4.12 DEFICIENCY DISEASE:
The main deficiency disease caused by lack of nicotinic acid is “pellagra”. This
disease affects epithelia & nervous system. It is accused by the accumulation of the
intermediate products of respiration; this is because nicotinic acid is required for the
synthesis of co-enzymes used by dehydrogenises. Nervousness, headaches, fatigue,
mental depression, skin, disorders, muscular weakness, & indigestion are the symptoms
of deficiency of niacin.
4.13 IDENTIFICATION TESTS FOR NIACIN (2)
1. Mix about 100 mg with 1 ml of dil NaOH solution & boil, no ammonia is
evolved (distinction from nicotinamide).
2. Mix about 100 mg with 10mg of citric acid & 3 drops of acetic anhydride &
heat on a water bath, a red – violet colour is produced.
Synonyms: - Acid Nicotinique (French), Acidum Nicotinicum, Akotin, Anti-pellagra

Vitamin, Apelagrin, Nico, etc.
4.14 PRECAUTIONS:
 The use of large doses of niacin for long periods causes release of histamine.
This in turn can cause severe flushing, severe itching of the skin and gastro
intestinal disturbances.
 If taken in does of 3gm per day, niacin has been reported to cause elevation of
uric acid in the blood and glucose.
37
4.14 NIACIN ANALOGUES:-
Tobacco products are considered to be predisposing factors in several forms of

cancer. Accordingly there are 43 carcinogenic substances in tobacco smoke, and nicotine
makes the use of tobacco products addictive. Smokeless tobacco (plug or leaf chewable
tobacco or snuff) is considered to be a predisposing factor in oral cancers (US Surgeon
General, 1986). Cadmium and nickel also have been implicated in the carcinogenicity of
tobacco products. Since removal of tar by filters and the use of smokeless tobacco do not
eliminate the risk of cancer associated with tobacco, the question remains "What are the
components of tobacco most responsible for the increased risks of cancer?" One obvious
possibility from our perspective is nicotine, itself, for its potential to interfere with
monooxygenase-catalyzed reactions in about five ways.
1. Nicotine is a known substrate of this monooxygenase, so this non-nutritive

compound can interfere directly with oxidations of regulatory substrates
catalyzed by this enzyme.
2. Nicotine is also a close structural analogue of nicotinamide and has the

potential for depleting NADPH by competitively inhibiting the absorption and
incorporation of the vitamin.
3. Theoretically, nicotine can also interfere with the production and redox
recycling of NADPH from NADP+, NAD+, and NADH.
4. In addition to the possibility of causing metabolic losses of NADPH,

nicotine may compete directly with NADPH for the monooxygenase and other
critical regulatory enzymic activities Consistent with this inhibitory potential is
the observation that porcine liver monooxygenase catalyzes the oxidation of
nicotine at a saturated maximum rate that is only 60 to 67% of that reported for
good substrates for this monooxygenase.
5. Finally, any depletion of NADPH by nicotine described, can result in an

additional irreversible inactivation of the monooxygenase by normal body
temperatures. The monooxygenase is highly vulnerable to thermal inactivation
under two very interesting circumstances:
38
1) When deprived of NADP+ and especially NADPH, or
2) When deprived of oxygen in the presence of NADPH. The latter

condition may exist in the center of rapidly growing tumors.
An interesting general feature about the regulation of biological systems is that

minor inhibition at any one step in a regulatory cascade (10% here, 10% there) can be
amplified by multiple affected sites along the entire pathway to produce dramatic
inhibition at the end point. The potential for cascade-amplified inhibition of the
monooxygenase with nicotine clearly exists. If nicotine proves to be a predisposing factor
through this proposed mechanism, nicotine patches will solve a tobacco consumer's risk
for cancer only if used to completely end the addiction.
4.15 VITAMIN B3 USES
Nicotinic acid, niacinamide, and inositol hexaniacinate (the three forms of

Vitamin B3) have all proved very successful in various clinical applications. However,
the forms of nicotinic acid and niacinamide consumed in access may prove to be
toxic.Conversely, inositol hexaniacinate has been supplemented in excess in scientific
studies and proved tolerable. Inositol hexaniacinate has been shown to lower elevated
LDL (bad cholesterol) and triglyceride (fat) levels in the blood, while concurrently
raising the HDL (good cholesterol) levels. Inositol hexaniacinate has also been used for
the prevention and treatment of peripheral vascular disease, especially intermittent
claudication (or the atherosclerosis of the blood vessels in the legs that can cause pain
with walking).Vitamin B3 may also be helpful in preventing the development of
atherosclerosis, and may aid in the reduction of complications arising from those who
suffer from specific heart conditions. As well, vitamin B3 may prove to be as effective as
prescription medications for treatment of atherosclerosis and problems associated with
the heart.
Niacin, specifically the form of niacinamide, has also been shown to provide
relief with complications resulting from diabetes. In a recent clinical study consisting of
343 individuals without diabetes and 125 with the disease, roughly 3000 milligrams per
day were administered. Hemoglobin A1C (a particular measure of blood sugar over a
period of time) actually decreased in the diabetic group over a 60-week follow-up period.
39
Further research is needed on niacinamide, but intial studies indicate its potentiality in the
treatment of arthritis. In addition, Vitamin B3 may reduce inflammation, increase joint
mobility, and may also aid in cartilage repair.
Eye health is another area of interest regarding the dietary supplementation of

niacin. In a recent study that included participants from the U.S. and Australia,
participants whose diets were supplemented with the highest amount of protein, Vitamin
A, B1, B2, and B3 (niacin) were considerably less likely to develop cataracts. Studies have
also shown riboflavin and niacin alone, to be effective in the prevention of cataract
formation. Ongoing applications of this B-vitamin compound include; vitamin
replacement in burn victims, topical solutions for acne, and as an anti-cancer agent.
Taking niacin with food may reduce stomach upset and the risk of stomach ulcer.
Doses are usually started low and gradually increased to minimize the common side
effect of skin flushing. Taking aspirin or non-steroidal anti-inflammatory drugs
(NSAIDs) at the same time during the first one to two weeks may reduce this flushing.
Use of an antihistamine 15 minutes prior to a niacin dose may also be helpful. The
flushing response may decrease on its own after one to two weeks of therapy. Extended
release niacin products may cause less flushing than immediate release (crystalline)
formulations, but may have a higher risk of stomach upset or liver irritation. In general,
not all niacin products are equivalent. Patients switching from one product to another
may have an increase or decrease in side effects.
Other Members of the Vitamin B Complex
Thiamine (B1), Riboflavin (B2), Pyridoxine (B6), Pantothenic Acid, Biotin,

Cyanocobalamin (B12). (23)
40
Chapter 5
IMPORTANTS OF NIACIN
Niacin deficiency symptoms can be seen in diets with niacin intake below 7.5 mg.
per day, but often this is not the only deficiency; vitamin B1, vitamin B2, and other B
vitamins, as well as protein and iron may be low. To treat pellagra and niacin deficiency
disorders, vitamin B3 supplements should be taken along with good protein intake to
obtain adequate levels of the amino acid tryptophan. As described earlier, about 50 % of
daily niacin comes from the conversion in our liver of tryptophan to niacin with the help
of pyridoxine (vitamin B6).
5.1 REQUIREMENTS:
Many food charts list only sources that actually contain niacin and do not take
into account tryptophan conversion into niacin. Approximately 60 mg. of tryptophan can
generate 1 mg. of niacin. But tryptophan is available for conversion only when there are
more than sufficient quantities in the diet to synthesize the necessary proteins as
tryptophan are used in our body with the other essential amino acids to produce protein.
Niacin needs are based on caloric intake. We need about 6.6 mg. per 1,000
calories, and no less than 13 mg. per day. Women need at least 13 mg. and men at least
18 mg. per day and for children ranges from 9-16 mg.
Niacin needs are increased during pregnancy, lactation, and growth

periods, as well as after physical exercise. Athletes require more B 3 than less active
people. Stress, illness, and tissue injury also increase the body's need for niacin. People
who eat much sugar or refined processed foods require more niacin as well.
Realistically, 25-50 mg. per day is adequate intake of niacin if minimum protein
requirements are met. On the average, many supplements provide at least 50-100 mg. per
day of niacin or niacinamide, which is a good insurance level. For treatment of the
variety of conditions described previously, higher amounts of niacin may be needed to
really be helpful, and levels up to 2-3 grams per day are not uncommon as a therapeutic
41
dose. The other B vitamins should also be supplied so as to not create an imbalanced
metabolic condition.
Excellent sources of vitamin B3 (niacin) include crimini mushrooms and tuna.

Very good sources include salmon, chicken breast, asparagus, halibut, and venison.
Vitamin B3, also commonly called niacin, is a member of the B-complex vitamin
family whose discovery was related to work by the U.S. Public Health Service in the
early 1900's. At that time, a disease called pellagra, characterized by cracked, scaly,
discolored skin, digestive problems, and overall bodily weakness was increasingly
prevalent in the southern region of the country. The Public Health Service established a
connection between the prevalence of the disease and cornmeal-based diets, and addition
of protein to these diets was found to cure many cases of pellagra.
Several years later, vitamin B3 was formally identified as the missing nutrient in
the cornmeal-based diets that had led to the symptoms of pellagra. We now know that
corn as a whole food contains significant amounts of vitamin B3, but that vitamin B3
cannot readily be absorbed from corn unless corn products (like cornmeal) are prepared
in a way that releases this vitamin for absorption.
For example, the use of lime (as in limestone, the mineral, not lime juice in the
fruit) can help release vitamin B3 from corn and make it available for absorption. Native
American food practices that involve the addition of ash from cooking fires ("pot ash" or
"potash") to corn-based recipes are one type of cooking technique that helps make
vitamin B3 available for absorption.
The term "niacin" used interchangeably with vitamin B3 is actually a non-

technical term that refers to several different chemical forms of the vitamin. These forms
include nicotinic acid and nicotinamide. (Nicotinamide is also sometimes called
niacinamide.) The names "niacin," "nicotinic acid," and "nicotinamide" are all derived
from research studies on tobacco in the early 1930's. At that time, the first laboratory
isolation of vitamin B3 occurred following work on the chemical nicotine that had been
obtained from tobacco leaves.
42
5.2 FUNCTION OF VITAMIN B3
Like its fellow B-complex vitamins, niacin is important in energy production.

Two unique forms of vitamin B3 (called nicotinamide adenine dinucleotide, or NAD, and
nicotinamide adenine dinucleotide phosphate, or NADP) are essential for conversion of
the body's proteins, fats, and carbohydrates into usable energy. Niacin is also used to
synthesize starch that can be stored in the body's muscles and liver for eventual use as an
energy source.
5.3 METABOLISM OF FATS
Vitamin B3 plays a critical role in the chemical processing of fats in the body. The
fatty acid building blocks for fat-containing structures in the body (like cell membranes)
typically require the presence of vitamin B3 for their synthesis, as do many fat-based
hormones (called steroid hormones).
Interestingly, although niacin is required for production of cholesterol by the

liver, the vitamin has repeatedly been used to successfully lower total blood cholesterol in
individuals with elevated cholesterol levels. This cholesterol-lowering effect of vitamin
B3 only occurs at high doses that must be obtained through nutrient supplementation, and
most likely involves a chemical feature of vitamin B3 that is not directly related to fat or
fat processing.
5.4 SUPPORT OF GENETIC PROCESSES
Components of the primary genetic material in our cells, called deoxyribose

nucleic acid (DNA) require vitamin B3 for their production, and deficiency of vitamin B3
(like deficiency of other B-complex vitamins) has been directly linked to genetic (DNA)
damage. The relationship between vitamin B3 and DNA damage appears to be
particularly important in relationship to cancer and its prevention.
43
5.5 DEFICIENCY SYMPTOMS
Because of its unique relationship with energy production, vitamin B3 deficiency

is often associated with general weakness, muscular weakness, and lack of appetite. Skin
infections and digestive problems can also be associated with niacin deficiency.
5.6 TOXICITY SYMPTOMS
Use of high-dose, supplemental niacin to lower serum cholesterol levels has given
nutritional researchers a unique opportunity to examine possible toxicity symptoms
associated with this vitamin. In the amounts provided by food, no symptoms of toxicity
have been reported in the scientific literature. In 1998, the Institute of Medicine at the
National Academy of Sciences set a tolerable upper limit (UL) for niacin of 35
milligrams. This UL applies to men and women 19 years or older, and is limited to niacin
that is obtained from supplements and/or fortified foods.
5.7 FACTORS THAT AFFECT FUNCTION
Intestinal problems, including chronic diarrhea, inflammatory bowel disease, and

irritable bowel disease can all trigger vitamin B3 deficiency. Because part of the body's B3
supply comes from conversion of the amino acid tryptophan, deficiency of tryptophan
can also increase risk of vitamin B3 deficiency. (Tryptophan deficiency is likely to occur
in individuals with poor overall protein intake.) Physical trauma, all types of stress, long-
term fever, and excessive consumption of alcohol have also been associated with
increased risk of niacin deficiency.
5.8 NIACIN PROTECTS AGAINST ALZHEIMER'S DISEASE AND AGE-

RELATED COGNITIVE DECLINE
Niacin (vitamin B3) is already known to lower cholesterol. Now, research

published in the August 2004 issue of the Journal of Neurology, Neurosurgery and
Psychiatry indicates regular consumption of niacin-rich foods also provides protection
against Alzheimer's disease and age-related cognitive decline.
Researchers from the Chicago Health and Aging Project interviewed 3,718
Chicago residents aged 65 or older about their diet, then tested their cognitive abilities
over the following six years. Those getting the most niacin from foods (22 mg per day)
44
were 70% less likely to have developed Alzheimer's disease than those consuming the
least (about 13 mg daily), and their rate of age-related cognitive decline was significantly
less. In addition to eating the niacin-rich foods, another way to boost our body's niacin
levels is to eat more foods rich in the amino acid tryptophan. Our body can convert
tryptophan to niacin, with a little help from other B vitamins, iron and vitamin C. Foods
high in tryptophan include shrimp, crimini mushrooms, yellow fin, tuna, halibut, chicken
breast, scallops, salmon, turkey and tofu. As we can see, several foods rich in tryptophan
provide two ways to increase niacin levels as they are also rich in the B vitamin. (August
23, 2004)
5.9 FORMS IN DIETARY SUPPLEMENTS
The term "niacin," often used interchangeably with the term "vitamin B3," is a
non-chemical term that can actually refer to several different forms of the vitamin. Most
often, "niacin" is used to refer to "nicotinic acid," the form of vitamin B3 with
documented cholesterol-lowering potential. This form of the vitamin also carries with it
the greatest risk of side effects. Supplements focused on cholesterol reduction and
alteration of fat metabolism typically include vitamin B3 in the form of nicotinic acid.
The nicotinamide form of vitamin B3 is also widely available in supplement form. This
chemical form of vitamin B3 carries a much lower risk of side effects and is commonly
used in supplement formulas designed to support health in conditions not involving
cholesterol excess or altered fat metabolism. Particularly in formulas for pregnancy or in
children's formulas, the nicotinamide version is often preferred. Many formulas include
both forms of vitamin B3, with small amounts of nicotinic acid and larger amounts of
nicotinamide.
5.10 INTRODUCTION TO NUTRIENT RATING SYSTEM CHART
In order to better help we identify foods that feature a high concentration of

nutrients for the calories they contain, we created a Food Rating System. This system
allows us to highlight the foods that are especially rich in particular nutrients. The
following chart shows the World's Healthiest Foods that are either an excellent, very
good, or good source of vitamin B3 (niacin). Next to each food name, we shall find the
serving size we used to calculate the food's nutrient composition, the calories contained in
45
the serving, the amount of vitamin B3 (niacin) contained in one serving size of the food,
the percent Daily Value (DV%) that this amount represents, the nutrient density that we
calculated for this food and nutrient, and the rating we established in our rating system.
For most of our nutrient ratings, we adopted the government standards for food labeling
that are found in the U.S. Food and Drug Administration's "Reference Values for
Nutrition Labeling."(25)
World's Healthiest Foods ranked as quality sources of:vitamin B3 (niacin)
World's
Nutrien
Serving Amount DV Healthiest
Food Cals t
Size (mg) (%) Foods
Density
Rating
26.
Crimini mushrooms, raw 5 oz-wt 31.2 5.39 15.6 Excellent
9
Tuna, yellowfin, 157. 67.
4 oz-wt 13.54 7.7 Excellent
baked/broiled 6 7
Tamari (Soy Sauce) 1 tbs 10.8 0.72 3.6 6.0 Good
223. 72.
Chicken breast, roasted 4 oz-wt 14.41 5.8 very good
4 0
187. 48.
Calf's liver, braised 4 oz-wt 9.61 4.6 very good
1 0
158. 40.
Halibut, baked/broiled 4 oz-wt 8.08 4.6 very good
8 4
Asparagus, boiled 1 cup 43.2 1.95 9.8 4.1 very good
Salmon, chinook, 261. 56.
4 oz-wt 11.34 3.9 very good
baked/broiled 9 7
179. 38.
Venison 4 oz-wt 7.61 3.8 very good
2 0
Romaine lettuce 2 cup 15.7 0.56 2.8 3.2 Good
229. 38.
Lamb loin, roasted 4 oz-wt 7.75 3.0 Good
1 8
214. 36.
Turkey breast, roasted 4 oz-wt 7.22 3.0 Good
3 1
Tomato, ripe 1 cup 37.8 1.13 5.6 2.7 Good
Mustard greens, boiled 1 cup 21.0 0.61 3.0 2.6 Good
112. 14.
Shrimp, steamed/boiled 4 oz-wt 2.94 2.4 Good
3 7
46
Summer squash, cooked,

1 cup 36.0 0.92 4.6 2.3 Good
slices
134. 16.
Green peas, boiled 1 cup 3.23 2.2 Good
4 1
119. 14.
Cod, baked/broiled 4 oz-wt 2.82 2.1 Good
1 1
Collard greens, boiled 1 cup 49.4 1.09 5.5 2.0 Good
Carrots, raw 1 cup 52.5 1.13 5.6 1.9 Good
Broccoli, steamed 1 cup 43.7 0.94 4.7 1.9 Good
Eggplant, cooked, cubes 1 cup 27.7 0.59 3.0 1.9 Good
0.25 207. 22.
Peanuts, raw 4.40 1.9 Good
cup 0 0
Spinach, boiled 1 cup 41.4 0.88 4.4 1.9 Good
Fennel, raw, sliced 1 cup 27.0 0.56 2.8 1.9 Good
Turnip greens, cooked 1 cup 28.8 0.59 3.0 1.8 Good
144. 14.
Spelt grains, cooked 4 oz-wt 2.91 1.8 Good
0 6
Beef tenderloin, lean, 240. 22.
4 oz-wt 4.44 1.7 Good
broiled 4 2
Raspberries 1 cup 60.3 1.10 5.5 1.6 Good
Winter squash, baked,
1 cup 80.0 1.44 7.2 1.6 Good
cubes
Swiss chard, boiled 1 cup 35.0 0.63 3.1 1.6 Good
Cauliflower, boiled 1 cup 28.5 0.51 2.5 1.6 Good
Kale, boiled 1 cup 36.4 0.65 3.3 1.6 Good
Green beans, boiled 1 cup 43.8 0.77 3.9 1.6 Good
Mustard seeds 2 tsp 35.0 0.60 3.0 1.5 Good
Cantaloupe, cubes 1 cup 56.0 0.92 4.6 1.5 Good
World's Healthiest Rule
Foods Rating
excellent DV>=75% OR Density>=7.6 AND DV>=10%
very good DV>=50% OR Density>=3.4 AND DV>=5%
good DV>=25% OR Density>=1.5 AND DV>=2.5%
47
Chapter 6
MATERIAL BALANCE
6.1 BASIS: 1 KG OF TOBACCO PER BATCH (18)
6.1.1 Mixing tank:-
5lit of H2O Mixer Wet slurry (6 Kg.)
1 Kg of Raw tobacco
Overall material balance over mixer
Water added + Raw tobacco = Wet slurry
5 lit of water + 1Kg of tobacco = Wet slurry
∴ Wet slurry = 6 Kg
As tobacco contains 5% nicotine
Material balance of nicotine
Let “X” be the quantity of nicotine in wet slurry
Nicotine in tobacco = Nicotine in wet slurry
0.05 X 1000 = X
∴ X = 50 gm
∴ Nicotine in wet slurry = 50 gm
48
6.1.2 Filtration:-
Wet Tobacco
Wet slurry [i.e.4Kg wet tobacco]
Filtration
(6 Kg)
Filtrate
(1400 ml)
Overall material balance
Wet Slurry in = Wet Tobacco + Filtrate + Loss
6000 = 4000 + 1400 + Loss
Loss = 600 ml
The wet tobacco after filtration can be dried and send to the cigarette
manufacturing unit to get non addictive cigarette.
6.1.3 Steam Distillation:-
Nicotine Solution
1400 ml of Steam 1040 ml
Distillation
Filtrate
Waste
360 ml

Filtrate = Nicotine Solution + Waste
1400 = 1040 + Waste
Waste = 360 ml
49
6.1.4 Separation:-
Nicotine layer
Nicotine solution Separator

(1040 ml)
Other constituents
Overall material balance over separator
Nicotine solution = Nicotine layer + other constituents
After measurement we get 1007 ml of other constituents from bottom of separator
1040 = Nicotine layer + 1007
Nicotine layer = 33 ml.
6.1.5 Oxidation Reaction:-
33ml of HNO3
Reaction
33ml of Reactor Product
110-115 0 C
Nicotine 30 min Niacin, Methylamine;
Oxalic acid & CO2
Overall material balance:

33 ml of HNO3 + 33 ml of Nicotine = Reaction Product
∴ Reaction Product = 45 gm.
The product from oxidation reaction in the form of precipitate was kept in the
accumulator for near about half hour. In the accumulator there was formation of two
layers due to density difference, the lower layer of Oxalic acid and upper layer of
Nicotinic acid, which was send to dryer.
50
Top Nicotinic acid

(45 gm) layer (36 gm)
Accumulator
Reaction
Product
Bottom Oxalic acid
layer (9 gm)
Reaction product = Top Nicotinic acid layer + Bottom Oxalic acid layer
45 = Top Nicotinic acid layer + 9
∴ Top Nicotinic acid layer = 36 gm
6.1.6 Drying:-
Moisture removed
Top Niacin layer Tray Dry Product
80 % Solid Dryer 95 % Solid

20 % Moisture 5 % Moisture
Let X and Y are the gm of water removed and product Niacin obtained.
Top Nicotinic acid layer = Dried product + Moisture removed
36 = X+Y
Solid balance
0.8 X 36 = 0.95 Y
51
Y = 30 gm
Nicotinic acid = 30 gm
X = 6 gm
Moisture removed = 6 gm
(18)
6.2 ENERGY BALANCE
6.2.1 Mixing Tank:
T = 250C Wet Slurry (6 Kg.)

Mixer at 60 0 C
5 lit H2O
1Kg of (T = 580C)
Tobacco
(T = 300C)
Amount of heat required to raise the temperature of tobacco mixture in mixing tank from
room temp. (i.e. 300C) to 600C
Q = m Cp ∆ T
Q = 6 X Cp X (60-30)
Approximate Specific heat capacity (Cp) values can be calculated for solids and
liquids by using a modified form of Kopp’s law, which is given by Werner (1941). (19)
Molecular formula of Nicotine is C1OH14 N2
Element Mol. Mass Heat capacity
C 120 120 X 7.5 = 900.0
H 14 14 X 9.6 = 134.4
N 28 28 X 26.0 = 728.0
162 1762.4
52
1762.4
∴ Specific heat = ------------ - = 10.88 J / g oc [ KJ / Kg 0C ]
Capacity 162
(Of Nicotine extract)
∴ Q = 6 X 10.88 X 30 = 1958.4 KJ
6.2.2 Steam Distillation:
Steam in
Feed Steam (110 0C)

1400 ml Product
Distillation
of filtrate
(280C)
Condensate
Amount of heat required in steam distillation section.
Q = m Cp ∆ T
= 1.4 X 10.88 X (110-28)
Q = 1249.024 KJ/hr
Amount of steam required is
Q = mCp ∆ T
1249.024 = m X 1 X (110-28)
∴ m = 15.232 kg/hr
∴ Amount of steam required was = 15.232 Kg/hr.
53
6.2.3 Oxidation Reactor:
Feed (30 0 C) Reactor 45 gm
33mlof Nicotine 1100C Product
33mlofHNO3
Amount of heat required in reactor is
Q = mCp ∆ T
Q = 0.066X10.88 X (110-30)
Q = 57.4464 KJ /hr
54
Chapter 7
REACTOR DESIGN
For 33 lit. of total reaction mixture.
V = 33 lit.
1m3 = 1000 lit.
= 33 lit.
For design purpose 10 % extra,
∴ V = 33 X 10-3 + 10 % Excess
∴ V = 36.3 X 10-3 m3
Diameter of reactor can be found out from volume of reactor; as we know.(16)
Volume = Area X Length --------------- (1)
Let, Diameter of reactor = D
Length of the reactor = L
Volume of the reactor =V
∴ Area of = π D2
Reactor 4
For plate thickness up to 50 mm (16)
L = 6
D
∴ Length of reactor = L = 6 D
Substituting area & length in equation (1)
∴ Volume = π D 2 X 6 D
4
∴ V = 1.5π D3
55
36.3X10-3 = 4.712 D 3
∴ D 3 = 7.7X 10-3
∴ D = 0.19 m
Di = 20 cm ≈ 200mm
Since L = 6
D
∴ L = 6 D = 6 X 20 = 120 cm
L = 1.2 m
P = 1atm
=101.325 X103 N/m2
Thickness is t = PD +C
D= 0.2 m
2fJ F = For Steel plate
The steel plate IS : 2041- 1962 allowable stress
3 3 = 3.5 X 106N/m2
= 101.325 X 10 X 0.2 + 1 X 10
J = 80%
2 X 3.5X106X 0.80
t = 4.62 mm ≈ 5mm
The Volume of metal used for constructing the vessel
v = t [π DL + π D 2 ]
2
-3
v = 5X 10 [0.754 +0.063]
v= 40.8 X 10-3 m3
56
Stoichiometric proportion of Nicotine & HNO3 for oxidation reaction (18)
According to the oxidation reaction
C10H14N2 + 9[O] --HNO3--- C6H5NO2 + C2H2O4.H2O + CH3NH2 + CO2
Nicotine Nascent Oxygen Nicotinic acid Oxalic Acid Ethylamine
1 mole of Nicotine ≡ 3 mole of HNO3
1X162 kg of Nicotine ≡ 3 X 63 kg HNO3
162 kg of Nicotine ≡ 189 kg HNO3
Specific gravity of Nicotine = 1.009
1.009 = Density of Nicotine

Density of H2O
1.009 = Nicotine
1 gm/cm3
∴ Density of Nicotine = 1.009 gm/cm3 = 1009 kg/m3
But Density = M i.e V = M = 162kg = 0.1605m3
V Density 1009 kg/m3
∴ Volume of Nicotine = 0.1605 m3 = 160.5 lit.
Volume of Nicotine = 160 lit.
Again specific gravity of HNO3 = 1.502
Density of HNO3
∴ 1.502 = ------------------
Density of H2O
∴ Density of HNO3 = 1.502 gm/cm3 = 1502 kg / m3
57
m 189 Kg
Volume of HNO3 = -------- = --------- = --------- = 0.1258 m3
1502 Kg/m3
∴ Volume of HNO3 = 0.1258 m3 = 125.8 lit
Volume HNO3 = 125 lit.
So for carrying oxidation reaction, take 1.6 ml of Nicotine & 1.25 ml HNO 3 to get
the desired product i.e. Nicotinic acid (Niacin). (18)
58
Chapter 8
COST ESTIMATION
8.1 COST OF EQUIPMENT:-
Sr.No Item Uni Cost / Total
. t Unit Cost(Rs.)
1 Pulverizer 1 200000 200000
2 Mixing Tank 1 3200000 320000
3 Filter press 1 480000 480000
4 Storage Tank 4 4000 16000
5 Steam Distillation 1 500000 500000
Setup
6 Condensor 1 100000 100000
7 Reactor 1 25000 25000
8 Dryer 1 150000 150000
Total ( E ) 1791000
8.2 FIXED CAPITAL INVESTMENT:-
8.2.1 Direct Cost:-

Sr.No Item % Cost
. E (Rs.)
1 Purchase Equipment Cost E 1791000
2 Equipment Installation 30 537300
3 Instrumentation & Control 15 268650
4 Piping Cost 15 268650
5 Electrical Fitting Cost 5 89550
6 Building Construction & Other 40 716400
Services
7 Yard Investment 3 53730
8 Land 30 537300
Total Direct Plant Cost (D) 4262580
59
8.2.2 Indirect Cost:-

Sr.No Item % Cost
. E (Rs.)
1 Engineering & Supervision 17 304470
Cost
2 Construction Expenses 32 573120
Total Indirect Cost ( I ) 877590
Total direct & indirect cost (I + D) = Rs. 5140170
Contractor Fees 5 % (I+D) = Rs.257000
Fixed Capital Investment (FCI) = Rs.5397170
Working Capital (WC) 20 % (I+D) = Rs.1028034
Total Capital Investment = FCI + WC
= 5397170 + 1028034
= Rs. 6425204
8.3 TOTAL PRODUCTION COST:-
8.3.1 Direct Production Cost:-
1) Raw Material Cost:-

Sr.No Raw Material Quantity/Batc Cost/ Kg Cost
. h (Rs.)
1 Waste Tobacco 500 Kg. Rs. 30 / Kg 15000
2 NaoH 5 Kg. Rs.180 / Kg 900
3 50 % HNO3 16.5 lit. Rs. 225 / 3713
lit.
Raw Material 19613
Cost
For one day three batches
Therefore raw material cost per day = 19613 X 3
60
= Rs. 58839
Raw material cost per month = 58839 X 30
= Rs. 1765170
8.3.2 Utilities:-
a) Water:-
Water requirement per batch = 25000 lit.
Cost of Water = Rs. 1 / lit.
Cost of Water per batch = Rs.2500
b) Steam:-
Requirement of Steam per batch = 900 Kg.
Cost of Steam = Rs. 5.33 / Kg.
Cost of Steam per batch = Rs. 4800
Cost of steam per day = 3 X 4800 = Rs. 14400
c) Electricity:-
Requirement of Electricity per batch = 800 Kwh
Cost of Electricity = Rs. 6 /Kwh
Cost of Electricity per batch = 800 X 6 = Rs. 4800
Cost of Electricity per Day = 3 X 4800 = Rs. 14400
B) Total cost of Utilities = 7500 + 14400 + 14400
= Rs. 36300 /day
Total cost of Utilities per month = 30 X 36300
= Rs. 1089000
61
8.4 OPERATING LABOUR COST:-

Post Number Salary / Total
month salary
General Manager 1 Rs. 15000 Rs. 15000
Engineer 2 Rs. 10000 Rs.20000
Skilled Worker 4 Rs. 5000 Rs.20000
Unskilled Worker 4 Rs. 3000 Rs.12000
Clerk 1 Rs. 3000 Rs.3000
Administrative 2 Rs.3500 Rs.7000
staff
Total Labour Rs.77000
Cost
Bonus = 0.3 X Total labour cost
= 0.3 X 77000
= Rs.23100
Operating labour cost per month = 77000 + 1925
O.L.C. = Rs. 78925 /month
Lab Charges = 10 % OLC
= 0.1 X78925
= Rs.7893 /month
Maintenance & repair = 0.5 % FCI
= 0.005 X 5397170
= Rs. 26986 / month
A) Direct production cost = Raw material cost + Cost of Utilities + Operating Cost + Lab
Charges + Main. & repair.
D.P.C. = 1765170 + 1089000 + 78925 + 78925 + 26986
= Rs. 2967974 / month
62
B) Depreciation & Taxes = 2 % FCI
= 0.02 X 5397170
= Rs. 107943
C) Insurance = 1 % FCI
= 0.01 X 5397170
= Rs. 53972
D) Distribution & Marketing = 20 % OLC
= 0.2 X 78925
= Rs.15785
E) Other Cost (R & D ) = 1 % FCI
= 0.01 X 5397170
= Rs. 53972
Total production cost per month = A + B + C + D + E
= 2967974 +107943 + 53972 + 15785 + 53972
= Rs.3199646
Now, 15 Kg Niacin, 15 Kg of Oxalic acid and 450 Kg of nonaddictive tobacco were

obtained from one batch process. Therefore for one month,
Niacin produced = 15 X 3 = 45 Kg / day
= 45 X 30 = 1350 Kg / month
Similarly Oxalic acid = 1350 Kg / month
And Nonaddictive tobacco = 450 X 3 X 30
= 40500 Kg / month
63
Sale:- (14)
Selling price of Niacin = Rs. 2100 / Kg
Selling price of Oxalic acid = Rs. 280 /Kg
Selling price of Tobacco = Rs. 15 / Kg
Monthly Sale:-
Niacin = 1350 X 2100 = Rs. 2835000
Oxalic acid = 1350 X 280 = Rs. 378000
Tobacco = 40500 X 15 = Rs. 607500
Total monthly sale = 2835000 + 378000 +607500
= Rs. 3820500
Gross profit = Total monthly sale - Total monthly production cost
= 3820500 – 3199646
= Rs. 620854
Income tax = 40 % Gross profit
= 0.4 X 620854
= Rs. 248342
Net profit = Gross profit – Income tax
= 620854 – 248342
= Rs. 372512 /month = 372512 X 12 = Rs. 4470144 /year
Rate of return on investment = Net profit per year
Fixed Capital Investment
= 4470144
5397170
= 0.83
Rate of return = 0.83
This evaluation is based on laboratory readings & previous literature on Niacin, so before
going for large scale production a test on pilot plant is necessary. (14)
64
Chapter 9
PLANT LAYOUT
After the process flow diagram was completed and before detailed piping design
and layout can begin, the layout of process unit must be planned and equipment within
these process unit must be planned. This layout can play an important role in determining
constructing and manufacturing cost; and thus must be planned carefully. Good plant
layout keeps safety, appearance, convenience, overall cost, erecting cost, operating and
maintenance cost to the minimum. Safety and optimum utilization of available area
should be given prime importance in plant layout. The key to economical construction
and efficient operation is a carefully planned functional agreement of equipment, piping
and building. An accessible and aesthetically pleasing plot plan can make major
contribution to safety, employee satisfaction and sound community relation.
The handling of the material is kept to minimum by provision of gravity

transportation wherever possible. Provision should be also made for necessary service
area; the administration or office building, canteen, workshops, laboratories, etc. The
main process plant should be isolated from administration building, canteen, workshops,
laboratories, etc, the storage tanks area, security room should be also isolated from main
plant. The canteen should also be neat to office building, laboratories; workshops etc.
process plant should be located on one side of a tank farm while shipping, transport, and
loading/unloading facilities on another side. Intermediate tanks should be located close to
the process unit. Administration and service facilities should be located near the process
plant entrance. Warehouses, salvage yard should be close together. Cooling towers
should be located where water drift from the tower will not cause excessive corrosion of
process equipment. They should be oriented cross way to the wind direction in order to
minimize recycling of air from the discharge of one tower to an adjacent tower. All
hazardous tank of larger size should be located at least 65m away from the building,
process plant, fired heaters. Pumping arrangement of liquid from the tank should be
decentralized. In process plant there should be sufficient space between the process
65
equipment. It avoids congestion after piping, valves, instrumentation is done on

equipment.
Storage Layout:-
Raw material storage tank should be located such that the transportation to the
process area is done easily loaded and unloaded.
Equipment Layout:-
Equipment should be installed in the process direction, maintaining reasonable

space between them. To consume space economically they should be arranged so that the
final product and initial reactants are near to storage tanks. The equipment should be
installed in the process direction in such a manner that handling of the material is kept to
minimum by provision of gravity transportation wherever it is possible; without
disturbing the main process.
Safety: -
Fire station should be located nearer to process area. In every unit hose pipes, fire
extinguisher should be placed.
Plant Expansion: -
Some space should be allocated for future expansion of the plant.
Utilities: -
Placing them nearer to the process area should effectively do distribution of

steam, power, water etc.
Administrative building: -
This should be located at the entrance of the main gate of the factory and there
must be provision made for communicating with every plant.
Laboratory and Quality Control: -
These should be located near the process plant. Due to which the evaluation
results and hence correction can be easily done within no time.
Commodities: -
66
Parking and canteen should be located near to the unit but not too close to the
unit. They should be separated from actual plant by the road.
Security Office: -
The security office and time office (checkers gate) should be located near to the
entrance of the factory.
In short the plant should fill the following points:
 More efficient use of land space.
 Lower cost of construction per square feet floor space.
 The upper stores building (e.g. administrative building etc) should be free
from street noise, dust, odor, etc).
 Use of gravity flow of materials, which is cheaper method of

transportation.
 More compact layout because of vertical arrangement of production area.
Market Area: -
Nicotinic acid is used by wider range of pharmaceutical industries. Major part of

nicotinic acid is exported and there were large transportation facilities in Ankalashawar .
Previously Amsal Chemical and their group is the only major manufacturer of nicotinic
acid. This provides opportunity to capture nearby market easily.
Raw Material Supply: -
Raw material required for production of Nicotinic Acid i.e. Waste Tobacco was
collected from tobacco farming nearby area and also from tobacco processing industries.
(13)
67
Chapter 10
CONCLUSION
Nicotinic acid is an antipellagra factor is a group of vitamin B3 . Majority sources
of it are Yeast, Rice polishing, Meatextract & Tobacco. By oxidation of tobacco with the
help of HNO3, nicotine is converted to nicotinic acid (Niacin). With this treatment to
tobacco the addictive nature of man towards tobacco becomes non-addictive & also
provide an improved tobacco product, so that blood plasma nicotine level resulting about
0 to 5 nanograms /ml. The main aim is to go for experimental work in lab-scale for
conversion of Nicotine to Nicotinic acid from Tobacco.It is a two step process,firstly
Extraction of nicotine from tobacco and secondly conversion of nicotine to nicotinic acid.
The reactor was to be designed for this oxidation process and the analysis of product &
by- products was to be carried out.
The objective of the process is to get non addictive tobacco product, the
poisonous Nicotine is converted to Vitamin B3, and to reduce the Carcinogenic effect of
tobacco on human health i.e. to get alternate use of tobacco for Nicotine Sulphate (as
pesticide), Niacin (Vitamin B3) pharmaceutical product, etc.
This invention relates in general to certain new and useful improvement in

processing of tobacco to eliminate or convert nicotine in the tobacco in to nicotinic acid
as a harmless or beneficial product such that the nicotine level which can be achieved by
use of the tobacco product result in a blood plasma level consonant with non-addiction.
The primary objects of the present invention is to provide a tobacco product adapted for
human use and which eliminates an addictive response to the user there of the another
object of the present invention to provide an improved tobacco product of the type which
utilized an oxidized tobacco in which nicotine has been converted to nicotinic acid or
extraction to a level resulting in the user is about 0 to about 5 nanograms per milliliter.
The another object of the present invention to provide an improved tobacco

product of the type stated in which a tobacco product is converted chemically or by
physical means to obviate any effects on the acetykholine brain receptors in an individual
smoking or otherwise ingesting such tobacco product.
68
In accordance with the present invention it has been found that by converting the
nicotine of a tobacco product in to a harmless and actually beneficial substance, such as
nicotinic acid, addiction to the tobacco product can be avoided. Thus the conversion of
the nicotine in accordance with the present invention not only elements the addiction but
also reduces some of the harmful effects of the identified as being generally recognized
as safe or approved. Nicotinic acid is also known as Niacin, Nicotineamide and anti
pellagra factor is a group of vitamin B3. Its compound was known before its vitamin
activity observed. It is widely used in the food, pharmaceutical & biochemical industries.
An odorless, white, crystalline substance, readily soluble in water. It is resistant to heat,
oxidation, and alkalis. It is, in fact, one of the most stable vitamins. Cooking causes little
actual destruction of niacin, but a considerable amount may be lost in the cooking water
and drippings from cooked meat if these are discarded. In a mixed diet, 15 to 25 percent
of niacin of the cooked food stuff may be lost in this way. It is excreted in the urine,
mostly as its salts, and to a smaller extent, as free niacin. The main deficiency disease
caused by lack of nicotinic acid is “pellagra”. This disease affects epithelia & nervous
system. It is accused by the accumulation of the intermediate products of respiration, this
is because nicotinic acid is required for the synthesis of co-enzymes used by
dehydrogenises. Nervousness, headaches, fatigue, mental depression, skin, disorders,
muscular weakness, & indigestion are the symptoms of deficiency of niacin.
Exposure to nicotine and combustible products from cigarette smoking is toxic to

renal function. In particular, nicotine has an adverse effect on behavior as it results in
people becoming addicted. Patients are predisposed to urinary tract cancers. Further
kidney damage can result from accumulation of heavy metals from tobacco. Associated
with altered renal function is a direct effect on nervous innervations, blood pressure and
blood vessels. Antismoking campaigns should be focused on achieving more success. For
instance, banning smoking in public venues and at workplaces will decrease the
deleterious effects of long-term exposure to nicotine. From 2nd Oct. 2008 it was banned to
smoke at public places and also at work places by the Government. Nicotine could also
be removed from combustion tobacco products. Alternatively nicotine-replacement
therapies may be used. One should avoid smoking by inhalation either actively or
passively
69
FUTURE PROSPECTS
1. With the help of this treatment to the tobacco the addictive nature of tobacco due to
Nicotine becomes non-addictive.
2. The harmful nicotine can be converted to Niacin.
3. The carcinogenic effect of tobacco due to nicotine can be reduced.
4. We can convert the harmful nicotine to the niacin which was pharmaceutical product.
5. For the waste coming from the tobacco industries & also from tobacco farming, this
was the important technique to get the valuable product.
6. The treated tobacco can also be used as a fertilizer for the farming purpose.
7. The main aim is to get alternative use of tobacco for Farmers due to the ban of
tobacco for beedi, hooka, chewing etc. by the Government.
8. To treat one cancer patient approximately Rs. 3.5 lacks required and near about 7.5
lacks people die due to cancer from tobacco, this can be avoided.
9. Due to commercialization of this process, the addictive tobacco becomes

nonaddictive and the pharmaceutical product Niacin can be produced.
10. By this method we can convert waste tobacco to the valuable pharmaceutical product
11. By optimizing the process the yield of Niacin from tobacco can be increased.
70
REFERENCES
1. Agarwal O.P. “Chemistry of Organic Natural Product”(2004) Volume I, Himalaya
Publishing House, (p.280,281).
2. Dr.Deb A. C. “Fundamentals of Biochemistry”(1990) A.Sen New Central

Book Agency, Calcutta,(p.191,192).
3. Kirk- Othmer “Encyclopedia of Chemical Technology”III rd ed.(1984)

Volume 24 A Wiley- Interscience Publication John Wiley & Sons (p.80-87).
4. Gurdeep Chatural “Organic Chemistry of Natural Products”(2004) Volume I

Himalaya Publishing House(p.571,573).
th
5. “The Pharmaceutical Codex” XI ed.(1979) The Pharmaceutical Press
London (p.593,594).
6. Harold Varley “Practical Clinical Biochemistry” IVth ed.(1969), CBS

Publisher & Distributors, Daryaganj New Delhi (p.622).
7. Richard J.Lewis Sr, Van Nostraud Reinhold “Hazardous Chemicals Desk

Reference” IInd ed. (2002),McGraw Hill Publication New York (p.844).
8. David L. Nelson & Michael M. Cox “Lehningers Principles of Biochemistry”

IVth ed (2005) W.H. Freeman & company New York (p.514, 515).
9. Finar I .L. “Organic Chemistry”(1994) Vth ed. Longman Singapore

Publishers Ltd. Singapore (p.717)
10. Douglas M. Considine “Chemical and Process Technology Encyclopedia”

(2004) Mc Graw Hill Book Company (page 71, 946).
11. Robert H. Perry, Don W. Green, “Perry,s Chemical Engineering Hand Book”
VIIth ed.(1997) Mc Graw Hill Publications,New York (p 2-41,42,43).
12. Larry Ricci & The Staff of Chemical Engineering “Seperation Techniques in
Liquid-Liquid System”.(2001) McGraw Hill Publications Co, New York
(p.552)
71
13. Khana O.P. “Industrial Engineering & Management” (1999), Dhanpat Rai
Publications (P.) Ltd.(p.4.1-4.35).
14. Peter Timmerhaus, West “Plant Design & Economics for Chemical
Engineers” Vth ed. (2004) Mc Graw Hill Publication, New York (p.323)
15. Warren L. McCabe, J.C. Smith, Peter Harriott, “Unit Operations of Chemical
Engineering V th ed. (1993) McGraw Hill Book Co. Singapore (p.614, 615).
st
16. Dr. S.D. Dawande “ Process Design of Equipments” I ed. (1999), Central
Techno Publications,Nagpur-12 (p.19,20).
rd
17. Robert E. Treybal “Mass– Transfer Operations”III ed. (1981) McGraw-Hill
Book Co. Singapore (p.717, 718,719).
18. Bhatt B.I. & Vora S.M. “Stoichiometry” III rd ed. (1998) Tata Mc Graw Hill
Publishing Company Ltd. (p.66, 67,187).
19. Richardson and Colusion. “Chemical Engineering Volume IV th ed.

“Chemical Engineering Design” (2008), Elsevier India Private Ltd.
(p.322,323).
20. http://icmr.nic.in/ijmr/2006/september/0905.pdf cited on 1/11/2006.
21. http://www.Properties of Tobacco.htm cited on 30/5/2008.
22. http://en.wikipedia.org/wiki/Nicotinicacid, cited on 25/10/2008.
23. http://www.Vitamin B3 Niacin Healthy Body,Healthy Mind, Holistic

Healing,Home Remedi, cited on 18/4/2008
24. http://Non-addictive tobacco products – Patents 5713376.htm cited on

22/9/2007.
25. http://www.purchon.com/biology/nicotinic acid cited on 3/3/2007.
26. http://www.Nicotine & its Derivatives from Tobacco Waste.htm, cited on

30/5/2008.
72
INDEX
Introduction to pervaporation 1
1.2 MEMBRANE BASED PERVAPORATION SEPARATION:.................................2
..........................................................................................................................................3
..........................................................................................................................................4
1.3 membrane material:...................................................................................................4
1.4 Nicotine content of tobacco:......................................................................................5
1.5 Tobacco waste sources:..............................................................................................5
1.6 Availability of tobacco waste:...................................................................................5
1.7 Chemical constituents of tobacco:.............................................................................5
1.8 Nicotine alkaloids of tobacco:...................................................................................6
1.9 Role of tobacco products in the economy: ................................................................6
1.10 Recommendations:...................................................................................................7
1.11 Properties of Tobacco Content:-..............................................................................8
1.12 DIESEASES FROM TOBACCO..........................................................................10
1.12 .1 Cancers of the urinary tract............................................................................10
1.12.2 Occupational exposure to cigarette smoke.....................................................10
1.12.3 Passive smoking..............................................................................................10
1.12.4 Nicotine induced nephropathies......................................................................11
1.12.5 Associated influence of nicotine on the nervous system................................11
1.12.6 Nicotine should be removed from combustion tobacco products..................12
Literature survey 13
2.1 Different methods for niacin....................................................................................13
2.1.1 Liquid phase oxidation of Nicotine using Chromic acid: - ..............................13
2.1.2 Liquid phase oxidation of MEP (2-methyl-5-ethylpyridine) with nitric acid or
air: - ...........................................................................................................................14
2.1.3 Liquid-Phase oxidation of 3-Picoline with Oxygen: - .....................................14
2.1.4 Gas phase oxidation of Picoline to Nicotinic acid: - ........................................15
2.1.5 Gas- Phase oxidation of Picoline to Cyanopyridine:- ......................................15
2.1.6 Commercial method followed by “Amsal Chemical Pvt. Ltd. Ankaleshwar:-.15
2.2 Review Article (20)..................................................................................................16
2.2.1 Effect of tobacco smoking on renal function:-.................................................16
2.2.2 Past work:..........................................................................................................16
2.2.3 Indian J Med Res 124, September 2006, pp 261-268.......................................17
2.3 NON-ADDICTIVE TOBACCO PRODUCTS (24)..............................................17
2.3.2. Brief Description of the Related Art ...............................................................18
2.4 OBJECTS ................................................................................................................20
2.5 SUMMARY OF THE INVENTION ......................................................................21
CONVERSION OF NICOTINE TO NICOTINIC ACID 25
3.1 Nicotine - sources and health aspects:-....................................................................25
3.1.1 Sources..............................................................................................................25
3.1.2 Main Reaction:..................................................................................................26
3.2 Physical Properties (11)...........................................................................................27
3.3 Process Description:- ..............................................................................................27
73
3.2.1 Nicotine consumption.......................................................................................28

3.2.2 Nicotine addiction and metabolism..................................................................29
NIACIN 30
4.1 History......................................................................................................................30
4.2 Dietary needs...........................................................................................................30
4.3 Properties: ..............................................................................................................30
4.3 Pharmacological uses:-............................................................................................31
4.4 Toxicity....................................................................................................................31
4.5 Biosynthesis.............................................................................................................32
4.6 Physical Properties of Nicotinic Acid (11)..............................................................33
4.7 Functions of Vitamin B3 Niacin:-............................................................................35
4.8 Chemical Structure (25)...........................................................................................35
4.9 Biological Synthesis ................................................................................................35
4.10 Sources...................................................................................................................36
4.11 Source Categories:.................................................................................................37
4.12 Deficiency Disease:...............................................................................................37
4.13 Identification Tests for NIACIN (2)......................................................................37
4.14 Precautions:............................................................................................................37
4.14 Niacin Analogues:-................................................................................................38
4.15 Vitamin B3 Uses....................................................................................................39
IMPORTANTS OF NIACIN 41
5.1 Requirements: ........................................................................................................41
5.2 Function of vitamin B3............................................................................................43
5.3 Metabolism of Fats ................................................................................................43
5.4 Support of genetic processes....................................................................................43
5.5 Deficiency Symptoms..............................................................................................44
5.6 Toxicity Symptoms..................................................................................................44
5.7 Factors that Affect Function....................................................................................44
5.8 Niacin Protects against Alzheimer's disease and Age-related Cognitive Decline...44
5.9 FORMS in Dietary Supplements.............................................................................45
5.10 Introduction to Nutrient Rating System Chart.......................................................45
MATERIAL BALANCE 48
6.1 Basis: 1 Kg of tobacco per BATCH (18).................................................................48
6.1.1 Mixing tank:-....................................................................................................48
6.1.2 Filtration:-.........................................................................................................49
6.1.3 Steam Distillation:-...........................................................................................49
...................................................................................................................................49
6.1.4 Separation:-.......................................................................................................50
6.1.5 Oxidation Reaction:-.......................................................................................50
6.1.6Drying:- .............................................................................................................51
6.2 Energy Balance (18) ........................................................52
6.2.1 Mixing Tank: ...................................................................................................52
6.2.2 Steam Distillation:............................................................................................53
6.2.3 Oxidation Reactor:............................................................................................54
Reactor Design 55
74
Cost Estimation 59
8.1 Cost of Equipment:-.................................................................................................59
8.2 Fixed Capital Investment:-.......................................................................................59
8.2.1 Direct Cost:-......................................................................................................59
8.2.2 Indirect Cost:-...................................................................................................60
8.3 Total Production Cost:-............................................................................................60
8.3.1 Direct Production Cost:-...................................................................................60
8.3.2 Utilities:-...........................................................................................................61
8.4 Operating Labour Cost:-..........................................................................................62
PLANT LAYOUT 65
CONCLUSION 68
Future Prospects.............................................................................................................70
REFERENCES 71
Index 73
75
LIST OF TABLE
SR. DESCRIPTION PAGE

NO. NO.
1 Liquid phase o`xidation reaction yields 10
2 Sources 22
3 Physical properties 24
4 Physical properties of Niacin 30
5 Food Sources 33
6 Worlds healthiest foods ranked as quality sources of 43, 44
Niacin
76

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Separation of Binary Mixture By Using Pervaporation

Compared with traditional separation processes, such as distillation, extraction

Figure 1.1 Schematic membrane separation processes

Figure 1.1 shows a schematic membrane process [Mulder 1991;

pervaporation, the liquid feed is separated into vaporous permeates

Pervaporation has become a very important technique to separate azeotropes, close-

1.2 MEMBRANE BASED PERVAPORATION SEPARATION:

It's considered an attractive alternative to other separation methods for a variety of

Figure 1.2 Overview of Pervaporation process

In addition, a pervaporation unit can be integrated into a bioreactor to improve

Figure 1.2.1: Membrane-based pervaporation separation processes Vacuum

1.3 MEMBRANE MATERIAL:

1.4 NICOTINE CONTENT OF TOBACCO:

Nicotine content is an important factor, which determines the quality of tobacco

1.5 TOBACCO WASTE SOURCES:

Tobacco waste or dust is generated at various stages of post harvest processing of

1.6 AVAILABILITY OF TOBACCO WASTE:

1.7 CHEMICAL CONSTITUENTS OF TOBACCO:

1.8 NICOTINE ALKALOIDS OF TOBACCO:

1.9 ROLE OF TOBACCO PRODUCTS IN THE ECONOMY:

1.11 PROPERTIES OF TOBACCO CONTENT:-

1. It is one of the gaseous elements found in tobacco smoke.

Factors governing the nicotine content of tobacco are:-

Nicotine is used in agriculture as an insecticide and in chemistry as a source of

1.12 DIESEASES FROM TOBACCO

1.12 .1 Cancers of the urinary tract

1.12.2 Occupational exposure to cigarette smoke

1.12.3 Passive smoking

Exposure to passive smoke is clearly a health risk. This includes an enhanced

1.12.4 Nicotine induced nephropathies

Nephropathies are accelerated by nicotine with an increased incidence of

1.12.5 Associated influence of nicotine on the nervous system

Renal injury induced by cigarette smoke condensate is reversed by renal

vasoconstriction in healthy non smokers, probably through alteration of a cyclic-GMP-

1.12.6 Nicotine should be removed from combustion tobacco products

Behavioural manipulations to reduce exposure to inhalation of cigarette smoke are

2.1.1 Liquid phase oxidation of Nicotine using Chromic acid: -

2C10H14N2 + 22CrO3 2C6H5NO2 + 8CO2 + 2NO2 + 9H2O + 11Cr2O3

Nicotine Chronic Acid Nicotinic Acid Chronic(III) oxide

2.1.2 Liquid phase oxidation of MEP (2-methyl-5-ethylpyridine) with nitric acid or

To avoid the problem of Picoline sourcing non-pyridine producers have used

i)Oxidation of MEP to Nicotinic acid (Niacin):-

C8H12N + 9[O] ---------- C6H5NO2 + 2CO2 + 3H2O

2-methyl-5-ethylpyridine Nicotinic acid

ii) Oxidation of MEP with Nitric acid:-

C8H12N + 6HNO3 ------ - C6H5NO2 + 2CO2 + 6H2O + 6NO

2-methyl-5-ethylpyridine Nicotinic acid

iii) Regeneration of Nitric Acid:-

3NO2 + H2O 2HNO3 + NO

Methyl ethyl pyridine (MEP) is itself produced by the liquid-phase condensation

2.1.3 Liquid-Phase oxidation of 3-Picoline with Oxygen: -

2.1.4 Gas phase oxidation of Picoline to Nicotinic acid: -

2.1.5 Gas- Phase oxidation of Picoline to Cyanopyridine:-

The gas phase ammoxidation to cyanopyridine followed by a hydrolysis

2.1.6 Commercial method followed by “Amsal Chemical Pvt. Ltd. Ankaleshwar:-

2.1.7 Finally, Niacin may be synthesized from pyridine:-

Bubbling CO 2 into a solution of pyridine and LiAlH4 in dioxane gives an 80-90%

2.2 REVIEW ARTICLE (20)

2.2.1 Effect of tobacco smoking on renal function:-

2.2.2 Past work:

2.2.3 Indian J Med Res 124, September 2006, pp 261-268

2.3 NON-ADDICTIVE TOBACCO PRODUCTS (24)