R16

III B.Pharmacy II Semister Regular Examinations, April/May-2019

PHARMACEUTICAL TECHNOLOGY-II

PART-A
1. a) Write a Raw material used for Preparation of hard gelatin capsules. (2M)
Ans:
Gelatin: It is prepared by the hydrolysis of collagen it is obtained from animal connective tissue,
bone and pork skin. It is two types such as type A (Acid hydrolysis of pork skin) & type B(
Alkaline hydrolysis of bones).
Certified dyes: Colour approved by D&C act
Opacifiers:TiO2
Plasticizers: Sorbitol & Glycerine
Preservative: Methyl & Propyl parabens
Sugar, Water and sulfur di oxide.
b) What are Micro capsules? Write their advantages. (2M)
Ans: Mono or multinuclear materials enclosed by a coat or membrane are called as
microcapsules. Microcapsules are characteristically free flowing powders consisting of proteins
or systemic polymers, which are biodegradable in nature and ideally having a particle size less
than 200 µm.
Advantages:
 Formulation of controlled release and sustained release formulations.
 Protection of the active agent or core material from environment.
 Liquids and gases can be changed in to solids in the form of Microcapsules.
 Surface and colloidal properties of some active agents can be altered.
c) Difference between dry and wet granulation methods. (2M)
Ans:
During wet granulation, liquid binders or adhesives are added to the lactose and active mixture,
usually by blending. The mixture is then dried and sized, and compressed into tablets. There by
producing a dust free formula plus improving flowability, eliminating poor content uniformity
and the ability to encapsulate a poorly soluble API.
During dry granulation, the particle size is enhanced by aggregating the particles by roller
compaction and then milling to the desired size, resulting in improved content uniformity,
dissolution times, and stability.
d) Write a problems involved in the film coating. (2M)
Ans:
 Picking and sticking
 Capping and lamination
 Twinning
 Molted colour
 Orange peel effect
 Filling
 Edge wear
 Film cracking
 Rough ness
 Blooming
e) Write a note on Non aqueous solvents used for parenteral products. (2M)
Ans: The commonly used non-aqueous vehicles are oils and alcohols. Fixed oil, such as, arachis
oil, cottonseed oil ,almond oil and sesame oil are used as vehicle .the oily vehicles are generally
used when a depot effect of drug is required or the medicaments are insoluble or slightly soluble
in water or the drug is soluble in oil example dimercaprol injection by using arachis oil as
vehicle. Ethyl alcohol is used in the preparation of hydrocortisone injection. hydrocortisone is
insoluble in water ,hence the solution is made in50% alcohol .Alcohol causes pain and tissue
damage at the site of injection . Therefore it is not used commonly. Propylene glycol is used as a
vehicle in the preparation of degoxin injection .it is relatively non-toxic but it causes pain on s/c
or I/M injection. sometime polyethylene glycol and glycerine usually diluted with sterile water
are used to prepare solutions for injections .they are used as solvent as well as to increase the
stability of certain preparations.
f) Write a ideal properties for packaging materials used for sterile pharmaceutical
formulations. (2M)
Ans:
 Protect the preparation from environmental conditions.
 Non-reactive with the product and so does not alter the identity of the product.
 Does not impart tastes or odours to the product.
 Nontoxic.
 FDA approved.
 Protect the dosage form from damage or breakage.
 Meet tamper-resistance requirements, wherever applicable.
 Adaptable to commonly employed high-speed packaging equipments
g) Write about types of glasses. (2M)
Ans:
Type I: Borosilicate Glass: Highly resistant glass and A substantial part of the alkali & earth
cations are replaced by boron and/or aluminum & zinc
Type II: Treated Soda-Lime Glass: Type II containers are made of commercial soda-lime glass
that has been de-alkalized or treated to remove surface alkali.
Type III – Regular Soda-Lime Glass: Containers are untreated & made up of commercial soda-
lime glass of average or better than-average chemical resistance.
Type NP – General Purpose Soda-Lime Glass: Containers made up of soda-lime glass are
supplied for non-parenteral products, those intended for oral or topical use.

PART-B

2. a) With a neat sketch explain the steps involved in manufacturing of soft-gelatin

capsules. (9M)
Ans: Rotary die process is most commonly used method for the manufacturing of soft gelatin
capsules.
Principle:
Involves the formation of a heat seal b/w two gelatin ribbons, simultaneous with dosing of fill
liquid into each capsule.
Typical Parts of Machine:
 Spreader Box
  Cooling Drum
 Oil Lubrication Roller
 Gelatin Ribbon Guide Roller
 Die Roll
 Injection Wedge
 Capsule Stripper
 Conveyor
 Medicine Filling Hopper
 Medicine Filling Pump
Working:
Two ribbons of gelatin are fed continuously into a rotating die assembly and are simultaneously
formed into the two halves of a capsule. The ribbons converge adjacent to a fill injector. The fill
injector is actuated by a pump which measures and dispenses the appropriate volume of fill
material into the capsules. The filled capsules are subsequently sealed as the die assembly
rotates. This process permits accurate and reproducible fill uniformity. Pump heads are available
for fill weights as low as 100 mg. For oral dosage forms, the fill weight ranges from 100 mg up
to about 1 gram.
The following should be monitored/controlled:
 Gelatin temperature
 Fill temperature
 Ribbon thickness
 Seal or seam width
Fill quantity following encapsulation, the capsules undergo drying in a tumble drying tunnel with
an elevated temperature and a large volume of forced air. From the drying tunnel, the capsules
are transferred onto trays and placed into a low humidity drying room.
The following should be monitored:
 Gelatin moisture
 Fill moisture
 Capsule hardness
Drying is a dynamic process, and the goal is to have the gelatin shell return to its equilibrium
moisture content in the range of 6 - 8%.
Oil fills dry faster than PEG fills, and typically reaches a shell moisture content of 6 to 8%
within 24 hours. If water migrates into the fill, it needs to migrate back out or at least be in
equilibrium with the moisture content of the shell for good stability. This is more typical of the
PEG fills. These can take 7 to 10 days to reach acceptable moisture levels, and may still contain
up to 10% water after drying.

Finishing:
After drying, the softgels are sorted (sized), polished, printed, and inspected for their quality. The
softgels are then packed into suitable containers, typically of low density polyethylene (LDPE)
bags, high density polyethylene (HDPE) bottles, or blisters. The recommended storage
conditions for the softgels include a temperature range of 15 – 300 C and a relative humidity of
not more than 50%. When stored under these conditions, the equilibrium moisture content of the
shell material and oxygen permeability through the material are minimal, thus improving the
stability of the softgel products.
b) Write a note on plasticizers and colorants used in capsule formulation. (5M)
Ans:
Plasticizers: These are added to the gelatin mass to confer softness, hardness, elasticity and
thickness to the capsule shell. The amount of plasticizer to be added depends upon the type of
capsule and storage conditions. These can be used alone or in combination with two or three
plasticizers. The hardness of gelatin shell is largely a function of dry plasticizer to dry gelatin
ratio. By varying the ratio, gelatin shells with varying degree of strength ranging from hard,
moderate to soft can be produced.
Colorants: Capsule shell may be clear and colourless, but to improve their elegance and to make
them distinctive and consumer appealing, certain FD & C and D &C approved dyes, pigments
and lakes are added to the gelatin mass. The colours however should not stain the capsulated fill
material.
3. a) Write in detail on centrifugal extrusion method for microencapsulation. (5M)
Ans:
Centrifugal extrusion method:
Centrifugal extrusion is another encapsulated technique that has been investigated and is
currently used by some vitamin manufacturers for the encapsulation of vitamin A acetate. The
device used in this encapsulation technique consists of a concentric feed tube through which
coating material and core material are pumped separately to the many nozzles mounted on the
other surface of the device. Core material flows through the centre of the tube; coating material
flows through the other tube. The entire device is attached to a rotating shaft such that the head
rotates around its vertical axis. As the head rotates, the core material and coating material are co-
extruded through the concentric orifices of the nozzles as a fluid 'rot' of core sheathed in coating
material. Centrifugal force impels the rod outward, causing it to break into tiny particles. By the
action of surface tension, the coating material envelops the core material, thus accomplishing
encapsulation. The capsules are collected on a moving bed of fine-grained starch, which
cushions their impact and absorbs unwanted coating moisture. Particles produced by this method
have diameters ranging from 150 to 2000 m.
A number of innovative, food approved coating systems have been formulated to encapsulate
products such as flavourings, seasonings, vitamins, and many others.
Another extrusion-based development from Southwest Research Institute is a process for
encapsulating of water-insoluble liquids as particles of 1 to 15 mm. In this process, a core
material is fed down a vertical tube. Simultaneously, the coating material, a viscous solution of
sodium alginate, flows through a ring-shaped opening around the base of the tube, forming a
membrane across the bottom of the device. The exuding core material bulges the membrane until
it eventually breaks off as an unshaped blob, carrying with it a portion of the membrane.
Spinning, the particles assume a spherical shape and become encapsulated. Passage through a
bath of aqueous calcium acetate (or calcium glutamate or calcium lactate) finishes the film-
forming process by converting the coating to water-insoluble calcium salt.
 Centrifugal extrusion process
b) Write in detail on coating material used for Microencapsulation. (9M)
Ans:
Microencapsulation often involves a basic understanding of the general properties of
microcapsules, Such as the nature of the core and coating materials, the stability and release
characteristics of the coated materials and the microencapsulation methods. The intended
physical characters of the encapsulated product and the intended use of the final product must
also be considered.
a. Core material: The core material, defined as the specific material to be coated, can be liquid
or solid in nature. The composition of the core material can be varied as the liquid core can
include dispersed and/or dissolved material. The solid core can be a mixture of active
constituents, stabilizers, diluents, excipients and release rate retardants or accelerators.
b. Coating materials: The coating material should be capable of forming a film that is cohesive
with the core materials, be chemically compatible and non-reactive with the core material and
provide the desired coating properties such as strength, flexibility impermeability, optical
properties and stability. The total thickness of the coatings achieved with microencapsulation
techniques is microscopic in size.
c. Stability, release and other properties: Three important areas of current microencapsulation
application are the stabilization of core materials, the control of the release or availability of core
materials and separation of chemically reactive ingredients within a tablet or powder mixture. A
wide variety of mechanisms is available to release encapsulated core materials; such as
disruption of the coating can occur by pressure, shear or abrasion forces, permeability changes
brought about enzymatically etc., improved gastro tolerability of drugs can be obtained by
microencapsulation.
d. Physical character of the final product: Microcapsules should have desirable physical
properties like ability to flow, to be compacted or to be suspended and the capsule wall must be
capable of resisting the pressure during compression etc.
e. coating materials: A number of different substances both biodegradable as well as non-
biodegredable have been investigated for the preparation or microcapsules. These materials
include the polymers of natural and synthetic origin and also modified natural substances.
Coating Material Properties:
 Stabilize the core material.
 Controlled release under specific conditions.
 Film-forming, pliable, tasteless, stable.
 Non-hygroscopic, no high viscosity, economical.
 Soluble in an aqueous media or solvent, or melting.
 The coating can be flexible, brittle, hard, thin etc.
Examples of Coating Materials:
1. Water soluble resin– Gelatine, Gum Arabic, Starch, Polyvinylpyrrolidone,
Carboxymethylcellulose, Hydroxyethylcellulose, Methylcellulose, Arabinogalactan, Polyvinyl
alcohol, Polyacrylic acid.
2. Water insoluble resins – Ethylcellulose, Polyethylene, Polymethacrylate, Polyamide (Nylon),
Poly (Ethylene- Vinyl acetate),cellulose nitrate, Silicones, Poly(lactideco- glycolide).
3. Waxes and lipids – Paraffin, Carnauba, Spermaceti, Beeswax, Stearic acid, Stearyl alcohol,
Glyceryl stearates.
4. Enteric resins – Shellac, Cellulose acetate phthalate, Zein.
5. Synthetic Polymers:
Non-biodegradable: PMMA , Acrolein, Glycidyl methacrylate , Epoxy polymers
Biodegradable: Lactides and glycolides and their copolymers, Polyalkyl cyano acrylates ,
Polyanhydrides, Corbopol
Natural Materials: Proteins, Albumins, Gelatin, Collagen, Carbohydrates, Starch, Agarose,
Carrageenan, Chitosan , Chemically modified carbohydrates, DEAE cellulose, Poly (acryl)
dextran, Poly (acryl) starch
4. a) Write about the ingredients used in tablet formulation. Write a note on wet
granulation method. (9M)
Ans: Ingredients used in tablet formulation
Tablet Ingredients In addition to active ingredients, tablet contains a number of inert materials
known as additives or excipients. Different excipients are:
 Diluent
 Binder and adhesive
 Disintegrents
 Lubricants and glidants
 Colouring agents
 Flavoring agents
 Sweetening agents
Diluent: Diluents are fillers used to make required bulk of the tablet when the drug dosage itself
is inadequate to produce the bulk. Secondary reason is to provide better tablet properties such as
improve cohesion, to permit use of direct compression manufacturing or to promote flow.
Commonly used tablet diluents: Lactose‐anhydrous and spray dried lactose, Directly
compressed starch, Hydrolyzed starch, Microcrystalline cellulose, Dibasic calcium phosphate
dehydrate, Calcium sulphate dehydrate, Mannitol , Sorbitol ,Dextrose.
Binders and Adhesives: These materials are added either dry or in wet‐ form to form granules
or to form cohesive compacts for directly compressed tablet.
Example: Acacia, tragacanth, Cellulose derivatives‐ Methyl cellulose, Hydroxy propyl methyl
cellulose, Hydroxy propyl cellulose , Gelatin, Glucose, Polyvinylpyrrolidone (PVP), Starch
paste, Sodium alginate, Sorbitol.
Disintegrants: Added to a tablet formulation to facilitate its breaking or disintegration when it
contact in water in the GIT.
Example: Starch, Starch derivative – Primogel and Explotab , Clays‐ Veegum HV, bentonite
sodium carboxy methyl cellulose, Alginate PVP (Polyvinylpyrrolidone),
Cross‐linked Superdisintegrants: Swells up to ten fold within 30 seconds when contact water.
Example: Crosscarmellose‐ cross‐linked cellulose, Crosspovidone‐ cross‐linked povidone
(polymer), Sodium starch glycolate‐ cross‐linked starch.
Lubricant and Glidants: Lubricants are intended to prevent adhesion of the tablet materials to
the surface of dies and punches, reduce inter particle friction and may improve the rate of flow of
the tablet granulation.
Glidants are intended to promote flow of granules or powder material by reducing the friction
between the particles.
Example: Lubricants‐ Stearic acid, Stearic acid salt ‐ Stearic acid, Magnesium stearate, Talc,
PEG (Polyethylene glycols), Surfactants
Glidants‐ Corn Starch – 5‐10% conc., Talc‐5% conc., Silica derivative ‐ Colloidal silicas such as
Cab‐O‐Sil, Syloid, Aerosil in 0.25‐3% conc.
Coloring agent: The use of colors and dyes in a tablets are used to masking of off color drugs ,
Product Identification and Production of more elegant product. All coloring agents must be
approved and certified by FDA. Two forms of colors are used in tablet preparation – FD &C and
D & C dyes.
Example: FD & C yellow 6‐sunset yellow, FD & C yellow 5‐ Tartrazine, FD & C green 3‐ Fast
Green, FD & C blue 1‐ Brilliant Blue, FD & C blue 2 ‐ Indigo carmine, D & C red 3‐ Erythrosin,
D & C red 22 – Eosin Y.
Flavoring agents: For chewable tablet‐ flavor oil are used .
Sweetening agents: For chewable tablets: Sugar, mannitol. Saccharine (artificial).
Wet granulation method
The wet granulation technique uses the same preparatory and finishing steps of direct
compression and dry granulation (dry screening and mixing); it also involve additional steps of
wet massing, wet screening and drying.
Steps involved in wet granulation
1. Mixing: Mixing starts with adding drug then excipients. The mixing process depends on the
properties of the drug and excipients. If the drug is soluble in water and excipients are little; so
we start to add binder solution to the drug to be distributed uniformly then excipients that have
little solubility in water (e.g. starch), it is possible to be added extragranularly [as a whole] or
[divided and added as one half intragranulary and the other extragranulary to avoid getting
friable tablets].
2.Wet massing: Adhesive (binder) is most commonly employed as solution, suspension, slurry,
or used as a dry powder. Method of introducing the binder depends on its solubility and on the
components of the mixture (wettability). In the wet massing step the binder solution will
distribute and filling the spaces between particles. Once the liquid is added, mixing is continued
until we get a uniform dispersion of the adhesive within the whole system.The length off wetting
time depends on the wetting property of the powder mix and the granulating fluid, and on the
efficiency of the mixer.
3.Wet screening:
Granulation is performed to obtain a discrete granules and further consolidate the granules by
increasing the particles contact points, and also to increase surface area to facilitate the drying
process.
4. Drying:
After drying step the granules should contain some degree of humidity to act as a binder (not be
100% free of humidity) as over drying may leads to weak force and friable granules.The final
cohesive force obtained after drying stage when evaporation of solvent occur as a result of
fusion, recrystalization and curing of the binding agent with Van der Waals forces playing a
significant role.
5. Dry screening: After drying; then dry screening is performed to get a homogenized granules
with uniform size and shape.
6. Mixing: By addition of lubricants and glidants. Therefore, the granules will posses good
compressibility (good cohesive forces once applying punch forming solid impact tab.), good
flowability (spherical shape that is the ideal physical form in providing smoothness and size
uniformity to the particles which is easily flow).
b)Write in detail on methods used for evaluation of tablet. (5M)
Ans: Evalution of Tablets:
1. General Appearance: The general appearance of a tablet, its identity and general elegance is
essential for consumer acceptance, for control of lot‐to‐lot uniformity and tablet‐to‐tablet
uniformity. The control of general appearance involves the measurement of size, shape, color,
presence or absence of odor, taste etc.
2. Size & Shape: It can be dimensionally described & controlled. The thickness of a tablet is
only variables. Tablet thickness can be measured by micrometer or by other device. Tablet
thickness should be controlled within a ± 5% variation of standard value.
3. Unique identification marking: These marking utilize some form of embossing, engraving or
printing. These markings include company name or symbol, product code, product name etc.
4. Organoleptic properties: Color distribution must be uniform with no mottling. For visual
color comparison compare the color of sample against standard color.
5. Hardness and Friability: Tablet requires a certain amount of strength or hardness and
resistance to friability to withstand mechanical shakes of handling in manufacture, packaging
and shipping. Hardness generally measures the tablet crushing strength.
6.Friability: Friability of a tablet can determine in laboratory by Roche friabilator. This consist
of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six
inches in the friabilator, which is then operate for 100 revolutions. The tablets are reweighed.
Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weigh are consider acceptable.
Drug Content and Release:
(I) Weight Variation test (U.S.P.): Take 20 tablet and weighed individually. Calculate average
weight and compare the individual tablet weight to the average. The tablet pass the U.S.P. test if
no more that 2 tablets are outside the percentage limit and if no tablet differs by more than 2
times the percentage limit.
(II) Content Uniformity Test: Randomly select 30 tablets. 10 of these assayed individually.
The Tablet pass the test if 9 of the 10 tablets must contain not less than 85% and not more than
115% of the labeled drug content and the 10th tablet may not contain less than 75% and more
than 125% of the labeled content. If these conditions are not met, remaining 20 tablet assayed
individually and none may fall out side of the 85 to 115% range.
(III) Disintegration Test (U.S.P.): The U.S.P. device to test disintegration uses 6 glass tubes
that are 3” long; open at the top and 10 mesh screen at the bottom end. To test for disintegration
time, one tablet is placed in each tube and the basket rack is positioned in a 1‐L beaker of water,
simulated gastric fluid or simulated intestinal fluid at 37 ± 2 0 C such that the tablet remain 2.5
cm below the surface of liquid on their upward movement and not closer than 2.5 cm from the
bottom of the beaker in their downward movement. Move the basket containing the tablets up
and down through a distance of 5‐6 cm at a frequency of 28 to 32 cycles per minute. Floating of
the tablets can be prevented by placing perforated plastic discs on each tablet. According to the
test the tablet must disintegrate and all particles must pass through the 10 mesh screen in the time
specified. If any residue remains, it must have a soft mass.
Disintegration time: Uncoated tablet: 5‐30 minutes
Coated tablet: 1‐2 hours
3.Dissolution Test (U.S.P.): Two set of apparatus:
Apparatus‐1: A single tablet is placed in a small wire mesh basket attached to the bottom of the
shaft connected to a variable speed motor. The basket is immersed in a dissolution medium (as
specified in monograph) contained in a 100 ml flask. The flask is cylindrical with a
hemispherical bottom. The flask is maintained at 37±0.50C by a constant temperature bath. The
motor is adjusted to turn at the specified speed and sample of the fluid are withdrawn at intervals
to determine the amount of drug in solutions.
Apparatus‐2: It is same as apparatus‐1, except the basket is replaced by a paddle. The dosage
form is allowed to sink to the bottom of the flask before stirring. For dissolution test U.S.P.
specifies the dissolution test medium and volume, type of apparatus to be used, rpm of the shaft,
time limit of the test and assay procedure for. The test tolerance is expressed as a % of the
labeled amount of drug dissolved in the time limit.
5. a)What is sugar coating? Write in detail on formulation and procedure involved in
sugar coating. (7M)
Ans: Sugar coating: Sugar coating is used in immediate release applications to mask unpleasant
taste and odour of some drugs or to improve aesthetic qualities of the product. It should be
understood that the coating process will add some time to the overall disintegration of the tablet
and may impact drug dissolution.
Formulation of Sugar coating: Because sugar-coating process consists of various steps, a
variety of additives may be incorporated into each type of formulation to achieve a particular
function. These include:
i. Sucrose, other sugars, and sugar alcohols: Sugars and sugar alcohols (such as glucose,
lactose, maltitol, mannitol, isomalt, sorbitol, xylitol, and sugar mixtures such as invert sugar and
starch sugars) for low calorie diabetic products (typically in the candy industry) and for the fact
that sucrose cause dental caries.
ii. Binders: Examples of binders used in sugar coating include polyvinyl acetate (PVA),
polyvinyl pyrrolidone (PVP), carboxymethyl starch, dextrin, acacia gum, gelatin, agar-agar,
sodium alginate, cellulose ethers, and starches.
iii. Fillers: E.g., precipitated calcium carbonate, talc, kaolin, dextrin, powdered acacia, corn
starch, and calcium sulfate.
iv. Colourants: Examples include dyes, lakes (aluminum lakes) and pigments (titanium dioxide
or other inorganic colouring agents).
v. Antiadhesives, Lubricants and Glidants: Examples include talc and colloidal silicon
dioxide.
vi. Flavouring agents: E.g., cinnamon, fruit flavours etc.
vii. Suspension stabilizers: Examples include surface active agents (emulsifying agents,
bentonite) or thickening agents.
viii. Smoothing agents: Example include a combination of syrup and acacia gum.
ix. Polishing agents: Beeswax and carnauba wax are good examples of polishing agents used in
sugar coating process.
Procedure involved in sugar coating: Sugar-coating process consists of various steps, each
designed to achieve a particular function. A typical sugar-coating process encompasses six
stages.
Sealing of the tablet core (Waterproofing/ Protective coating): Seal coating involves the
application of specialized polymer-based coating (either by ladle or spray techniques) directly to
the tablet core. It is an optional step but is usually required to prevent the tablet core and its
contents from absorbing water, softening, and initiating disintegration during the subsequent
steps of the sugar-coating process. Sealing also prevents certain types of materials (e.g. oils,
acids, etc.) from migrating to the tablet surface and spoiling the appearance.
Sub coating: This step is regarded as the first major step in sugar-coating process. It involves the
application of large quantities of sugar-coatings to the tablet core, significantly increasing the
tablet weight by 50 – 100 %. Sub coating provides the rapid buildup necessary to round up the
tablet edge. It also provides the foundation for smoothing and colour coating with any weakness
in the final sugar coat often being attributable to weaknesses in the sub coat.
Smoothing or Grossing: In order to manufacture quality sugar-coated tablets, it may be
necessary to smooth out the tablet surface and fill the irregularities generated during subcoating.
Smoothing usually can be accomplished by applying sucrose-based solution with or without
additional components such as starch and calcium carbonate. This is followed by drying until the
tablets are properly rounded and smooth. Drying may last up to 20 minutes or more depending
on the scale of operation.
Colour coating/ Colouring: This is one of the most important steps in the sugar-coating process
as it has immediate visual impact that is associated with overall quality. It involves the multiple
application of syrup solutions (60–70% sugar solids) containing the requisite colouring materials
necessary to achieve the desired shade. As with film coating colours, sugar-coating colourants
may be subdivided into either water-soluble dyes or water-insoluble pigments. The nature of the
colourant selected often defines the type of colour-coating procedure to be used.
Polishing/ Glossing: Sugar-coated tablets are, by nature very dull in appearance (i.e., they have
a matte surface finish), and thus requires a separate polishing step to give them the high degree
of gloss that typifies finished sugar-coated tablets. Polishing is accomplished by applying
mixtures of waxes either as powders (usually in a finely milled form) or as solutions/dispersions
in various organic solvents to the coated tablets in a polishing pan.
Printing: It is common practice to identify all oral solid dosage forms with a product name,
company name or logo, dosage strength or other distinctive symbol. For sugar-coated tablets,
such identification involves the application of special edible inks to the coated tablet surface by
means of a printing process known as offset rotogravure.
b) Write in detail on solvents used in preparation of tablet coating materials. (7M)
Ans: Solvents play an important role in the formulation of coating solution. They serve as a
vehicle for dissolving and dispensing the constituents of coating solution and help in the
application of coating on the tablet surface.
Examples of commonly used solvents are water, alcohols (ethanol, methanol, isopropanol),
ketones( acetone, methyl ethyl ketone), chlorinated hydrocarbons( chloroform, trichloroethane,
methylene chloride) and esters (ethyl acetate, ethyl lactate).
An ideal solvent should possess the following characteristics,
 It should be colourless, odourless and tasteless
 It should be inexpensive and non toxic
 It should be inert and non- explosive
 It should be compatible with other additives and should easily dissolve or disperse them.
 It should not show any environmental hazards
 It should have a faster rate of drying
Water is consider to be an ideal solvent, since it is readily available and does not cause any
environmental hazard. Most of the polymers do not effectively dissolve in water and many drugs
undergo hydrolysis, therefore organic solvents are considered to be a better option.
For a good film is necessary that there should be good interaction between the polymer and the
solvent, so that a find of good mechanical and adhesive properties is obtained.
6. Write short notes on (14 M)
i) Additives used in parentral product formulation.
ii) Sterility testing of injectable.
Ans:
i) Additives used in parentral product formulation:
Additive substances or additives are generally employed in parenteral preparation to enhance its
physical and chemical stability i.e shelf life or esthetic appearance.
Types of Parenteral Additives:
Anti-microbial agents: A suitable preservative system is required in all multiple dose parenteral
products to inhibit the growth of microorganism accidentally introduced during withdraw of
individual doses. Preservatives may be to single dose parenteral products that are not terminally
sterilized as a sterility assurance measure i.e. to prevent the growth of any microorganism that
could be introduced of there were any inadvertent breach of asepsis during filling operations.
Example: Benzalkonium chloride, Benzethonium chloride, Benzyl alcohol, Phenol, Metacresol
Antioxidants: Many drugs in solutions are subject to oxidative degradation. Such reaction are
mediated by free radicals or by molecular oxygen or removal of hydrogen . Oxidative
decomposition is catalyzed by metal, hydrogen and hydroxyl ions. Drugs possessing a favorable
oxidation potential will be especially vulnerable to oxidation. For example, a great number of
drugs are formulated in the reduced form (e.g. epinephrine, morphine, ascorbic acid, e.t.c.) and
are easily oxidized.
Buffers: Many drugs require a certain pH range to maintain product stability. Drug stability
strongly depend on the pH of the solution. Buffer system for parenterals consist of either a weak
base or a salt of weak base or a weak acid or salt of weak acid.
Example: Acetic acid , Adipic acid, Citric acid, Sodium bicarbonate, Sodium carbonate
Chelating agents: Chelating metals are added to complex and thereby inactivate metals such as
copper, iron, zinc that generally catalyze oxidative degradation of drug molecules. Sources of
metal combination include raw material impurities solvents such as water, rubber stoppers, and
containers and equipment employed in the manufacturing process.
Example: Edetate disodium , Edetate tetrasodium
Inert gases: Another means of enhancing the product integrity of oxygen sensitive medicaments
is by displacing the air the solution with nitrogen or argon. This technique may be made more
effective by first purging with nitrogen or boiling the water to reduce dissolved oxygen. The
container is also purged with nitrogen or argon before filling and may also be topped off with gas
before sealing.
Solubilizing, wetting agents: Solubilizing agents are used to increased drug solubility by using
non aqueous solvents.
Example: Polyethlene glycol, Ethyl alcohol , Glycerin , Lecithin , povidone
Surfactants: Surfactants are used to dispose a water insoluble drugs as a colloidal dispersion and
to prevent crystal growth in a suspension ,to provide acceptable syringability.
Example: Polyethylene, Sorbitan monooleate
Tonicity adjustment agents: Isotonicity is important for parenteral preparation because the
possibility that the product may penetrate red blood cell and cause hemolysis is greatly reduced
if the solution is isotonic with blood i.e. the cells maintain their tone. Solution that less osmotic
pressure than the blood plasma called hypotonic and solution that more osmotic pressure than the
blood plasma called hypertonic. When introduce hypotonic solution cell may swell and offers
brust because of diffusion of waterinto the cell i.e. hemolysis, if introduce hypertonic solution
,the cell may lose water and shrink.in sotonic solution the cell maintain their tone and the
solution is isotonic with human erythrocytes.
Example: Sodium chloride, Gelatin, Lactose, Dextrose, Sorbitol
Protectants: Protectants are used to protect against loss of activity caused by some stress and to
prevent the loss of active ingredients by adsorption to process equipment or to primary
packaging material Protectants are used in the formulations of proteins.
Example: Sucrose, Glucose, Maltose, Lactose
ii) Sterility testing of injectables
The test for sterility is carried out under aseptic conditions. In order to achieve such conditions,
the test environment has to be adapted to the way in which the sterility test is performed. The
precautions taken to avoid contamination are such that they do not affect any microorganisms
which are to be revealed in the test. The working conditions in which the tests are performed are
monitored regularly by appropriate sampling of the working area and by carrying out appropriate
controls.
The sterility test carried out by following two methods
Membrane filtration: Use membrane filters having a nominal pore size not greater than
0.45 µm whose effectiveness to retain microorganisms has been established. Cellulose nitrate
filters, for example, are used for aqueous, oily and weakly alcoholic solutions and cellulose
acetate filters, for example, for strongly alcoholic solutions. Specially adapted filters may be
needed for certain products, e.g. for antibiotics. The technique described below assumes that
membranes about 50 mm in diameter will be used. If filters of a different diameter are used the
volumes of the dilutions and the washings should be adjusted accordingly. The filtration
apparatus and membrane are sterilized by appropriate means. The apparatus is designed so that
the solution to be examined can be introduced and filtered under aseptic conditions; it permits
the aseptic removal of the membrane for transfer to the medium or it is suitable for carrying out
the incubation after adding the medium to the apparatus itself. Alternatively, transfer the medium
onto the membrane in the apparatus. Incubate the media for not less than 14 days.
Direct inoculation of the culture medium: Transfer the quantity of the preparation to be
examined prescribed in Table 2 directly into the culture medium so that the volume of the
product is not more than 10% of the volume of the medium, unless otherwise prescribed. If the
product to be examined has antimicrobial activity, carry out the test after neutralizing this with a
suitable neutralizing substance or by dilution in a sufficient quantity of culture medium. When it
is necessary to use a large volume of the product it may be preferable to use a concentrated
culture medium prepared in such a way that it takes account of the subsequent dilution. Where
appropriate the concentrated medium may be added directly to the product in its container. Oily
liquids. Use media to which have been added a suitable emulsifying agent at a concentration
shown to be appropriate in the method suitability of the test, for example polysorbate 80 at a
concentration of 10 g/l. Ointments and creams. Prepare by diluting to about 1 in 10 by
emulsifying with the chosen emulsifying agent in a suitable sterile diluent such as peptone (1 g/l)
TS1. Transfer the diluted product to a medium not containing an emulsifying agent. Incubate the
inoculated media for not less than 14 days. Observe the cultures several times during the
incubation period. Shake cultures containing oily products gently each day. However when fluid
thioglycollate medium is used for the detection of anaerobic microorganisms keep shaking or
mixing to a minimum in order to maintain anaerobic conditions.
Observation and interpretation of results:
At intervals during the incubation period and at its conclusion, examine the media for
macroscopic evidence of microbial growth. If the material being tested renders the medium
turbid so that the presence or absence of microbial growth cannot be readily determined by
visual examination, 14 days after the beginning of incubation transfer portions (each not less
than 1 ml) of the medium to fresh vessels of the same medium and then incubate the original and
transfer vessels for not less than 4 days.
7. a) Write a detail on various plastics used for pharmaceutical product packaging. Add a
note on their advantages and disadvantages. (9M)
Ans: According to British standards institutes plastics represents; A wide range of solid
composite materials which are largely organic, usually based upon synthetic resins or upon
modified polymers of natural origin and possessing appreciable mechanical strength. At a
suitable stage in their manufacturing, most plastics can be cast, molded or polymerized directly
into shape.
Types of plastic materials
Thermoplastic type: On heating, they are soften to viscous fluid which hardens again on
cooling. Resistant to breakage and cheap to produce and providing the right plastics are chosen
will provide the necessary protection of the product in an attractive containers. E.g. polyethylene,
PVC, polystyrene, polypropylene, polyamide, polycarbonate.
Thermosetting type: When heated, they may become flexible but they do not become liquid.
During heating such materials form permanent crosslinks between the linear chains, resulting in
solidification and loss of plastic flow. E.g. Phenol formaldehyde, urea formaldehyde, melamine
formaldehyde.
Most commonly used packing materials:
Polyethylene:
 This is used as high and low density polyethylene
 Low density polyethylene (LDPE) is preferred plastic for squeeze bottles. Properties: Ease
of processing , barrier to moisture, strength /toughness, flexibility, ease of sealing.
 High density poly ethylene (HDPE) is less permeable to gases and more resistant to oils,
chemicals and solvents.
Polypropylene:
 It has good resistance to cracking when flexed.
 Good resistance to heat sterilization.
 It is colorless, odorless thermoplastic material with excellent tensile properties even at high
temperature.
 Excellent resistance to strong acids and alkalis.
Polyvinyl chloride (PVC):
 Versatility, ease of blending, strength / toughness, resistance to grease/oil, resistance to
chemicals, clarity.
 Used as rigid packaging material and main component of intravenous bags.
 Drawback: Poor impact resistance which can be improved by adding elastomers to the
plastics but it will increase its permeability.
Polystyrene:
 Versatility, insulation, clarity, easily foamed (“Styrofoam”).
 It is also used for jars for ointments and creams with low water content.
 Drawback: Chemicals like isopropyl myristate produce crazing(a fine network of surface
cracks) followed by weakening and eventually collapsible of the container.
Advantages of plastic materials
 Low in cost
 Light in weight
 Durable
 Pleasant to touch
 Flexible facilitating product dispensing
 Odorless and inert to most chemicals
 Unbreakable
 Leak proof
 Able to retain their shape throughout their use
 They have a unique suck-back feature, which prevents product doze.
 Ease of transportation
 They are poor conductor of heat.
 They are resistant to inorganic chemicals.
 They have good protection power.
Disadvantages
 Plastics appear to have certain disadvantages like interaction, adsorption, absorption
lightness and hence poor physical stability.
 All are permeable to some degree to moisture, oxygen, carbon dioxide etc and most exhibit
electrostatic attraction, allow penetration of light rays unless pigmented, black etc.
b) Write a note on evaluation of rubber containers. (5M)
Ans:
Preparation of sample solution (A):
 Wash closures in 0.2%w/v of anionic surface active agents for 5min.
 Rinse 5 times with dist water and add 200ml water and is subjected to autoclave at 119 to
123⁰C for 20 to 30min covering with aluminum foil.
 Cool and separate solution from closure (soln-A)
Evaluation tests
Penetrability: This is measured to check the force required to make a hypodermic needle
penetrate easily through the closure. It is measured by using the piercing machine. The
piercing force must not exceed a stated value. If it exceeds that stated value, the hypodermic
needle can be damaged as a result of undesirable hardness of the closures.
Fragmentation test: This test is performed on 20 closures. Each closure is penetrated with
hypodermic needle in a piercing machine five times within a limited area and needle is washed to
transfer any fragment present. The contents are filtered through coloured paper that contrasts
with the rubber and the fragments counted. On an average there should not be more than three
fragments per unit.
Self sealability test: Applicable to multidose containers fill 10 vials with water close them with
prepared closures and secure with a cap. For each closure use a new hypodermic needle and
pierce 10 times each time at different site immerse the vials upright in methylene blue (0.1%)
solution and reduce external pressure for 10 minutes. Restore the atmospheric pressure and leave
the vials immersed for 30 minutes. Rinse the outside of the vials. None of the vials contains any
trace of coloured solution.
Extractive test: In this test, the closure is boiled with water for four hours under reflux and the
water evaporated to dryness. The residue must not exceed the specified amount.
Compatibility test: This test is performed to check the compatibility of the rubber closures with
various types of the substances, since it is necessary to ensure that there is no interaction
between the contents of the bottle and the closure.
Light absorption Filter solution A through membrane filter. Measure the light absorbance of
filtrate in the range 220 to 360 nm using a blank solution (prepared in the same manner as
solution A). The absorbance is not more than2.
Light absorption: Filter solution A through membrane filter. Measure the light absorbance of
filtrate in the range 220 to 360 nm using a blank solution (prepared in the same manner as
solution A). The absorbance is not more than 2.