Rezi Riadhi Syahdi

Analisis
Farmasi Dasar
z
Tujuan Perkuliahan

Mahasiswa mampu menjelaskan definisi analisis, pemisahan, pemurnian

dan uji kemurnian

Mahasiswa mampu menjelaskan jenis-jenis dan aplikasi pemisahan analitik

Mahasiswa mampu menjelaskan jenis-jenis dan aplikasi metode analisis

kualitatif

Mahasiswa mampu menjelaskan jenis-jenis dan aplikasi tetapan fisika dan

uji kemurnian pada bahan baku farmasi

Mahasiswa menentukan pemisahan analitik, metode analisis kualitatif,

tetapan fisika, dan uji kemurnian yang tepat ketika diberikan masalah
analisis
z
Materi Perkuliahan

Metode Pemisahan Analitik: Ekstraksi, Filtrasi, Dekantasi,

Sublimasi, Rekristalisasi, Sentrifugasi, Destilasi, Kromatografi

Metode Analisis Kualitatif: Analisis Unsur dan Gugusan

Tetapan Fisika dan Uji Kemurnian

z
Buku Referensi

Vogel Textbook of Quantitative Inorganic Analysis

Christian Analytical Chemistry

Stahlled Laboratory Handbook

Snyder And Kirland. Introduction to Modern Liquid

Chromatography
 What is Analytical Chemistry?
z

Concerned with the chemical characterization of

matter and the answer of :
1) What is it (Qualitative) identification of
elements, ions or compound
2) How much is it (Quantitative)

everything is made of chemicals. Analytical

chemists determine what and how much
 Separation process
z

almost every element or compound naturally

found in an impure state

these impure raw materials must be separated

into their purified components before they can be
put to productive use

a separation process is used to transform a

mixture of substances into two or more distinct
products.
 zImportant in synthesis, chemical industries,
biomedical

The separated products could differ in chemical

or physical properties, such as size, or crystal
modification or other separation into different
components

The mixture at hand could exist as a combination

of any two or more states: solid-solid, solid-liquid,
solid-gas, liquid-liquid, liquid-gas, gas-gas, solid-
liquid-gas mixture, etc.
 Separation isolate the analyte from interfering constituents

z Separation can be either complete or partial

Complete separation

A B C
Mixture ABC

Partial separation

Mixture AB C
Mixture ABC
 Classifying separation techniques
z

Separation based on .

Size filtration, dialysis, ion-exchange chromatography

Mass/density (if there is diff. in the mass/density) centrifuge
Complexation reaction masking
 z

Change of state (if an analyte and interferent in the same phase)

distillation, sublimation, recrystallization, precipitation
Partitioning between phase (analyte and interferent are in two
immiscible phases) extraction, chromatography
 z

A chemical analysis (esp. quantitative) is

ordinarily performed in duplicate or
triplicate.

Each vessel that holds a sample must be

marked so that its content can be
positively identified.

Flask, beaker and some crucibles have

small etched areas on which semi
permanent mark can be made with a
pencil.
 Types of Analytical Balances
z
An analytical balance is a weighing instrument with a maximum capacity
that ranges from 1 g to a few kilograms with a precision of at least 1 part in
105 at maximum capacity.
Macrobalances have a maximum capacity ranging between 160 and 200
g; measurement can be made with a standard deviation of 0.1mg.
Semimicroanalytical balances have a maximum load of 10 to 30 g with
a precision of 0.01mg.
Microanalytical balance has a capacity of 1 to 3 g and a precision of
0.001mg.
 z
Rules for Handling Reagents and
Solutions
1. Select the best grade of chemical available for analytical
work.
2. Replace the top of every container immediately after
removal of the reagent.
3. Hold the stoppers of reagent bottles between your fingers.
4. Never return any excess reagent to a bottle.
5. Never insert spatulas, spoons, or knives into a bottle that
contains a solid chemicals.
6. Keep the reagent shelf and the laboratory balance clean
and neat.
7. Observe regulations concerning the disposal of surplus
reagents and solutions.
 Cleaning and Marking Laboratory Ware
z

Every beaker, flask, or crucible that will contain the

sample must be thoroughly cleaned before being
used.
The apparatus should be washed with a hot detergent
solution and then rinsed, initially with tap water and
finally with several small portions of deionized water.
Organic solvents such as benzene or acetone may be
used to remove grease films.
z

Standard taper glassware, especially the round bottom flask, is

susceptible to star cracks
 z
Desiccators and Desiccants
Oven drying is the most common way of removing moisture from solids.
This approach is not appropriate for substances that decompose or for
those from which water is not removed at the temperature of the oven.

Dried material are stored in desiccator while they cool so as to minimize

the uptake of moisture. The base section of the desiccator contains a
chemical drying agent (desiccants) such as anhydrous calcium chloride,
calcium sulfate, magnesium perchlorate or phosphorus pentoxide.
z

Desiccator
 z Heating Equipment
Many precipitate can be weighed directly after being
brought to constant mass in a low temperature drying
oven. Such an oven is electrically heated and capable
of maintaining a constant temperature to within 1 oC.
The maximum attainable temperature ranges from 140
to 260oC, depending on make and model, for many
precipitate 110oC is a satisfactory drying temperature.
Microwave laboratory ovens are currently appearing
on the market. Where applicable, these greatly
shorten drying cycles.
Muffle furnace (a heavy duty electric furnace) is capable of maintaining controlled temperatures
of 1100oCzor higher. Long handled tongs and heat resistance gloves are needed for protection.
 Introduction to Analytical Separations
Introduction

1.) Sample Purity

Many chemical analysis are not specific for one compound
- Actually respond to many potential interferences in the sample

Often it is necessary to first purify the compound of interest

- Remove interfering substances before a selective analysis is possible
- This requires a separation step.

2.) Techniques available for Chemical Separations:

Extraction
Distillation
Precipitation
Chromatography
Many others (centrifugation, filtration, etc)

Extractions and Chromatography are especially useful in analytical methods

 Introduction to Analytical Separations
Introduction

3.) Illustration
Biological Samples are Composed of Complex Mixtures
- Analysis of composition and changes help in understanding disease and the
development of treatments
NMR Spectra of Mouse Urine
after treatment with a Drug Analysis of Various Pesticides
in Ground water using LC-MS 2D Gel Electrophoresis of total
protein extract from E. coli cells

Journal of Chromatography A,
Toxicological Sciences (2000) 57:326-337 1109 (2006) 222227 Electrophoresis (1997) 18:1259-1313
 Introduction to Analytical Separations
Extractions

1.) Definition
The transfer of a compound from one chemical phase to another
- The two phases used can be liquid-liquid, liquid-solid, gas-solid, etc
- Liquid-liquid is the most common type of extraction

Immiscible
[ S ]2
K
liquids

[ S ]1
- The partitioning of solute s between two chemical phases (1 and 2) is
described by the equilibrium constant K

K is called the partition coefficient

 Introduction to Analytical Separations
Extractions

2.) Extraction Efficiency

The fraction of moles of S remaining in phase 1 after one extraction can be
determined
- The value of K and the volumes of phases 1 and 2 need to be known

V1
q
V1 KV2
where: q = fraction of moles of S remaining in phase 1
V1 = volume of phase 1
V2 = volume of phase 2
K = partition coefficient

The fraction of S remaining in phase 1 after n extractions is

n
V1
qn Assumes V2 is constant

1 V KV
2
 Introduction to Analytical Separations
Extractions

2.) Extraction Efficiency

Illustration

Ether layer

Water layer

1M UO2(NO3)2
(yellow)

After mixing, UO2(NO3)2 After 8 extractions, UO2(NO3)2

Is distributed in both layers has been removed from water
 Introduction to Analytical Separations
Extractions

4.) Example #1:

Solute A has a K = 3 for an extraction between water (phase 1) and benzene
(phase 2).

If 100 mL of a 0.01M solution of A in water is extracted one time with 500 mL

benzene, what fraction will be extracted?

Solution:
First determine fraction not extracted (fraction still in phase 1, q):

n 1
V1 100 mL
qn 0.062 6.2%
V1 KV2 100 mL ( 3 ) ( 500 mL )

The fraction of S extracted (p) is simply:

p 1 q 1 0.062 0.938 93.8%

 z
Tugas Kelompok

Bagilah kelas menjadi 7 kelompok, buatlah presentasi @10 menit

untuk menjawab pertanyaan berikut

a. Berikan definisi tentang (1) filtrasi dan dekantasi (2) Sublimasi dan
destilasi (3) rekristalisasi, dan (4) sentrifugasi dan ekstraksi

b. Jelaskan aplikasinya dan bagaimana langkahnya dalam memisahkan

(1) Magnesium hidroksida, asam salisilat, dan natrium sulfat dalam
air (2) metanol dengan air dan naftalen dengan lilin (3) asam benzoat
terkontaminasi CuSO 4 (4) susu skim dan pemisahan DNA dari darah

c. Powerpoint dikumpulkan dalam format .pptx melalui surel ke

rezi.riadhi@farmasi.ui.ac.id paling lambat Sabtu, 2 September 2017
Pukul 23.59 WIB dengan format AFD_nomorkelompok.pptx
Pipets and syringes Transfer pipet
Dont blow out the last drop
TC 20oC = calibrated to contain the Measuring (Mohr) pipet
indicated volume at 20oC (ambient
Microliter pipet (Eppendorf)
temperature)
E : eingu
TD 20oC = calibrated to deliver the
indicated volume at 20oC
A : ausgu

The coefficient of expansion for dilute

aqueous solution: 0.025%/oC

VT1 = VT2 + 0.00025(T1-T2)VT2

where T1 > T2

Pipets and sylinder.

 z
Volume Measurement

Pipets

Burets

Volumetric flask

Measuring cylinder
Transfer pipet.
Measuring (Mohr) pipet.
Microliter pipet with disposable plastic tip.
Volume selection dial of microliter pipet.
Repeater pipet, which can deliver preset volumes between 10 L and 5 mL to 48
times at 1-s intervals without refilling.
z
Hamilton syringe
Digital dispenser for syringes with volumes of 0.5 to 500 microliter provides accuracy
and precision of 0.5%
Pipet fillers and pipets
1. Latex bulb
2. Pipet filler
3. Mechanical pipet filler
4. Pipettor pump
5. Pasteur pipet

6. Volumetric pipet
7. Mohr pipet
8. Serological pipet
Safety rubber bulb filler and auto-filler
A 1 2 3 4

E S

Safety rubber bulb filler

A : press on valve A and squeeze bulb
S : Insert pipet into liquid sample. Press on valve
S. Suction draws liquid to desired level.
E : Press on valve E to expel liquid sample.
To deliver the last drop, maintain pressure on
valve E, cover E inlet with middle finger, and
squeeze the small bulb.
z
z

Automatic pipet
z

Burets and volumetric flask

z

Reading a buret
z

Using pipet
z

Titration
 z
Weighing by Difference
Weighing by difference is a simple method for determining a series of
sample weights. First the bottle and its contents are weighed. One sample
is then transferred from the bottle to a container; gentle tapping of the
bottle with its top and slight rotation of the bottle control over the amount
of sample removed. Following transfers are weighed. The mass of the
sample is the difference between the two weighings.
z
Simple Crucibles
Simple crucibles serve only as containers.
Porcelain, aluminum oxide, silica and platinum
crucibles maintain constant mass and are used
principally to convert a precipitate into a suitable
weighing form. The solid is first collected on filter
paper. The filter and contents are then transferred
to a weighed crucible, and the paper is ignited.
z
Physical Methods of Separation

Only separate the different substances in a mixture.

No new substance is formed.

The choice of separation

technique depends on the
nature of the mixture.
 Various Methods for Separating
the Components of a Mixture
Chromatography: separating components
of a mixture that have differing adsorptive
tendencies on a stationary phase as the
mixture is passed over or through the
stationary phase . Chromatography of
plant pigments

Distillation: Separation through

vaporization of a liquid from a solid, or
another liquid, followed by vapor
condensation.
Distillation is used in many different industries
including chemical, brewery and pharmaceutical.
 Filtration: removing a solid substance from a liquid by
passing
z the suspension through a filter.

Crude oil filtration

Gravity (vacuum filtration)
Filtration

Decantation: a process for separating the liquid component

of a solidliquid mixture from the solid by pouring.

Decanting whey Decanting

from the curds a solvent
in cheese making. from a solute.
Crystallization: forming a Sublimation
crystalline solid by of
decreasing its solubility as Iodine
a result of cooling the
solution, evaporating the
solvent, or adding a
solvent in which the solid
is less soluble such that
solid crystals form.

Sublimation:
vaporizing a solid
and subsequently
Crystals of insulin grown in space
let scientists determine the vital
condensing its
enzyme's structure and linkages
with much higher resolution than
Earth-grown crystals.
mineral vapor.
aquamarine
 z
Extraction: removing a
substance from a solid or
liquid mixture by adding a
solvent in which the
substance is more soluble.

Centrifugation: removing a
substance from a solution
by means of a centrifuge.
z
Filtration

Solid-Liquid Mixture
 Filtration
z

Solid-liquid mixture (insoluble solids) E.g.

sand in water
A filter paper is used because it contains very
tiny pores.

Mixture of solid
and liquid
z

Ashless filter-paper :
Specially treated filter-paper (pulps treated by using 6M HCl, HF)
that leaves a negligible residue(=incombustible matter) after
ignition. Ash 0.2mg when a filter-paper(I.D. 11cm) has been
incinerated.
 z
Filter Paper
Paper is an important filtering medium. Ashless paper
is manufactured from cellulose fibers that have been
treated with hydrochloric and hydrofluoric acids to
remove metallic impurities and silica, ammonia is then
used to neutralize the acids. It is necessary to destroy
the paper by ignition if the precipitate collected on it is
to be weighed.
z

Folding and seating a filter paper

z
 z
Filtering Crucibles
Filtering crucibles serve not
only as containers but also
as filters. A vacuum is used
to hasten the filtration, a
tight seal between crucible
and filtering flask is
accomplished with any of
the several types of rubber
adapters.
 z
Sintered-glass Crucibles
Sintered-glass crucibles are manufactured in fine,
medium, and coarse porosities. The upper temperature
limit for sintered glass crucible is ordinarily about
200oC. Filtering crucibles made entirely of quartz can
tolerate substantially higher temperatures.
Gooch crucible
Filtering crucible
Separating funnel

Crucibles
z

Vacuum Filtration
Train for vacuum filtration
Vacuum filtration with a Gooch crucible that has a porous (fritted) glass disk through
which liquid can pass. Suction can be applied by the vacuum system or by an aspirator
that uses flowing water to create vacuum. The trap prevents backup of tap water from the
aspirator into the suction flask. Alternatively, the trap prevents liquid in your suction flask
from being accidentally sucked into the vacuum system.
 z
Sieving

a porous material is used to separate particles of different sizes.

method is most commonly used to effect gross separations, as of liquids

from suspended crystals or other solids.

to accelerate filtration, pressure usually is applied.

a series of sieves is stacked, with the screen of largest hole size at the
top
 z
Decantation

Decanting is done to separate particulates from a liquid by

allowing the solids to settle to the bottom of the mixture and
pouring off the particle-free part of the liquid. Another method is
to allow two immiscible liquids to separate and the lighter liquid is
poured off.
 z
Decanting
Materials:
Beakers - 150 and 250 mL
Matter Samples C and A
Deionized water
Graduated cylinder
Stirring rod
(Left) Filtering a precipitate. The conical funnel is supported by a metal or wood ring
attached to a ring stand. (Center) Washing by decantation. (Right) Transferring the
precipitate.
Creeping is a process in which a solid moves up the side of a wetted container or filter
paper.
 Solubility Charts Are Useful for
Separating Components of a Mixture
Cold Hot 3M 3M
water water HCl NaOH

Benzoic acid No Yes No Yes

Mg(OH)2 No No Yes No

Na2SO4 Yes Yes Yes Yes

Zn(OH)2 No No Yes Yes

The differing solubility of a compound in various

solvents can be used to separate the compounds.
 Soluble in H2O Reacts with 3M HCl *TODAYS EXPERIMENT:
SiO2 No No
2.5 to 3.0 grams
NaCl Yes No unknown only.
CaCO3 No Yes

10.00 g* of
SiO2 + NaCl + CaCO3

Step 1?
Filtrate?
Residue?

2.
 Soluble in H2O Reacts with 3M HCl *TODAYS EXPERIMENT:
SiO2 No No
2.5 to 3.0 grams
NaCl Yes No unknown only.
CaCO3 No Yes

10.00 g* of
SiO2 + NaCl + CaCO3

1. Add Water
Filtrate
Residue
NaCl (aq) SiO2 (s) + CaCO3 (s)
1.80 g
Step 2?
Filtrate? Residue?
 Soluble in H2O Reacts with 3M HCl *TODAYS EXPERIMENT:
SiO2 No No
2.5 to 3.0 grams
NaCl Yes No unknown only.
CaCO3 No Yes

10.00 g* of
SiO2 + NaCl + CaCO3

1. Add Water
Filtrate
Residue
NaCl (aq) SiO2 (s) + CaCO3 (s)
1.80 g
2. React with HCl
Filtrate Residue

CaCl2 (aq) SiO2(s)

3.20 g
Step 3?
Filtrate? Residue?
 Soluble in H2O Reacts with 3M HCl *TODAYS EXPERIMENT:
SiO2 No No
2.5 to 3.0 grams
NaCl Yes No unknown only.
CaCO3 No Yes

10.00 g* of
SiO2 + NaCl + CaCO3

1. Add Water
Filtrate
Residue
NaCl (aq) SiO2 (s) + CaCO3 (s)
1.80 g
2. React with HCl
Filtrate Residue

CaCl2 (aq) SiO2(s)

3. React with K2CO3 3.20 g
Filtrate Residue
KCl (aq) CaCO3 (s)
4.10 g
 Soluble in H2O Reacts with 3M HCl *TODAYS EXPERIMENT:
SiO2 No No
2.5 to 3.0 grams
NaCl Yes No unknown only.
CaCO3 No Yes

10.00 g* of
SiO2 + NaCl + CaCO3

1. Add Water
Filtrate
Residue
NaCl (aq) SiO2 (s) + CaCO3 (s)
1.80 g
2. React with HCl
Filtrate Residue
How many grams
were recovered? CaCl2 (aq) SiO2(s)
What is the Percent 3. React with K2CO3 3.20 g
Recovery? Filtrate Residue
KCl (aq) CaCO3 (s)
4.10 g
 CRYSTALLISATION

Separating soluble solids from a solution

z
Crystals are solids that have
a definite regular shape
smooth flat faces and straight
edges
Crystallization is the process of
forming crystals
 z
Crystallization

Separation technique that results in

the formation of pure solid particles
from a solution containing the
dissolved substance
As one substance evaporates, the
dissolved substance comes out of
solution and collects as crystals
Produces highly pure solids
z Crystallisation

Maximum amount
To separate dissolved pure solid from a solution.
of solid dissolved
in a given solvent.

2. Saturated solution

Evaporation of solution

3. Pure Crystals formed.

1. Heat the solution

until saturated.
Evaporation can
be used to
separate a solute
from the solvent
in a solution
 z
Materials:
Sample
Balance
Beaker - 150 mL
Deionized water
Graduated cylinder
Conductivity indicator
Evaporating dish
Tongs
Hot Plate
Watch glass

Turn the hot plate on before evaporating Sample

Turn the hot plate OFF when liquid is evaporated.
z
How to test for saturated solution?
Dip a glass rod into the solution and removed.

If crystals are formed on the glass rod, it means that the solution
is saturated.

This is the saturation point or crystallisation point.

 z Recrystallization
Impure benzoic acid

Benzoic acid after recrystallization

 Dissolve sample in hot solvent
z

Compound crystallizes upon cooling

z
Impure benzoic acid in hot water
 Add water and heat until
z
all soluble material
dissolves

Insoluble material is removed by

filtration
 z Crystals form in the warm solution

Next:
Cool, filter, wash, dry, weigh, mp
 Summary
z

Insoluble Purified
Soluble
impurities benzoic acid
impurities
 Fractional Crystallization
z
z
Reflection

Why cant we just evaporate the solution to dryness to obtain

the crystals?

For some substances, they will decompose when heated.

charring

When water is removed, any soluble impurities will be left on the

crystal not pure.
z
Simple Distillation

Separating liquid from a solution

z
Distillation
To separate a liquid from a solution.

E.g. Ethanol, sucrose

Involves two physical state changes.
 z Set-up for distillation Main concept
Boiling point of the liquid
Bulb of thermometer placed beside
the side arm of the distillation flask to
ensure accurate measurement of
1 boiling point.
Liquid is heated until
its boiling point and
2
changes to vapour.
Vapour is cooled
and changes to
liquid (distillate).

Mixture

To ensure smooth
boiling.
Other examples:
1. Marble chips
2. Porcelain chips
 z Boiling chips

To ensure smooth boiling

During boiling of water, big air bubbles can be seen.

These air bubbles causes bumping.

Boiling chips can reduce this bumping effect.

 z
Temperature Profile

Temperature remains unchanged

until all the liquid boils off.

Temperature as
solution is heated
z
Disadvantage of Simple Distillation
Unable to separate liquids who boiling point differ by less than
20C.

Use fractional distillation!

z
Fractional Distillation

Separating miscible liquids

z
Fractional distillation

For liquids that are miscible and having different boiling

points.
Miscible mix together completely to form a solution. E.g. water
and ethanol
Liquid with lower boiling point distill over first.
Liquids with higher boiling point will return back into the round-
bottomed flask.
 z
Set-up of fractional distillation
Main concept
Boiling point of the liquids
where the liquid with the
lowest boiling point
Thermometer Water outlet will distill over first.

Condenser
Fractionating
column

Round-bottomed flask
Water inlet
Liquid-liquid mixture
Distillate

Boiling chips
 z
During fractional distillation,
The liquid with lowest boiling point will
distill over to the condenser first.

The vapour of liquids with higher boiling

point condenses along the fractionating
column and re-enter the round-bottomed
flask.
 z
Fractionating Column

Packed with glass beads

Provide large surface area for

evaporation and condensation of
liquids with different boiling points
for effectively separation.
 What is the difference between distillation and fractional
z distillation?

Simple distillation Fractional

Distillation
No fractionating Has a fractionating
column column
Separate liquids Able to separate
whose boiling points liquids whose boiling
differs more than point differs by less
20C than 20C
z
Critical Thinking

Is it possible to obtain salt from seawater?

Yes

However, industrially, we use reverse osmosis to obtain salt

(Desalination). What is the reason?

Distillation exhaust a lot of energy, resulting in high

production cost.
z
z
 Steam Distillation
z

The distillation of two immiscible liquids in which one of the

immiscible liquid is water, the process is called as Steam
Distillation."
The immiscible liquid and water boil at high temperature.
However, when steam is passed through the mixture of these
liquids, then they boil at a much lower temperature. (Even less
then the boiling point of water).
Many organic compounds which are insoluble in water can be
separated and purified by this process, but at much lower
temperature then their original boiling point. For example,
Turpentine oil has boiling point 160C, but when it is mixed with
water, it can be distilled at a temperature of 75C, which is below
the boiling point of water.
Similarly Bromo-Benzene has normal boiling point 156.2C.
When it is mixed with H2O, it is distillated at a temperature of
61C which is below the normal boiling point of water.
 Process
z
The apparatus used for steam distillation consists of a steam
container, flask or still, receiver and condenser. The steam
container has two holes. Safety tube is fitted in one hole and
reaches the bottom. Another tube is fitted in the other hole which
carries the steam into the still or flask. The safety tube must reach
the bottom of the container. If the pressure rises of the steam
becomes to much to be controlled, then extra steam comes out
through this tube.

The mixture of immiscible liquids is placed in the still or flask.

The flask and the steam container are heated simultaneously, so

that a rapid current of steam passes through the boiling mixture.
The vapors are allowed to pass through condenser.

Distillation is continued till the whole mixture is collected in the

receiver. The distillate in the receiver has two layers, one aqueous
and other non-aqueous, which are then separated from each
 THE EQUIPMENT
z
 Applications
z
of Steam Distillation

Some applications of steam distillation are as

follows:
1- Many organic compounds can be purified
without decomposition by steam distillation.
2- Volatile oils can be extracted from crude
oils by steam distillation.
3- Aromatic water is prepared by this process.
"Aromatic Water: Aromatic water is defined as
the saturated solution of volatile substances."
For example, Anise water, Chloroform Water,
Rose water.
z
Centrifugation
When there is only a small amount of
suspension, or when much faster
separation is required
Centrifugation is often used
instead of filtration
Centrifugation
z

The liquid containing

undissolved solids is put
in a centrifuge tube
The tubes are then put
into the tube holders in a
centrifuge

A centrifuge
Centrifugation
z

The holders and tubes are spun around at a

very high rate and are thrown outwards
The denser solid is collected as a lump at
the bottom of the tube with the clear liquid
above
 z SUBLIMATION

Sublimation is the process in which transforming

the solid to vapors without intermediate passage
through the liquid state.

Triple point.
Triple point is the point having a definite
temperature and pressure at which the solid,
liquid and vapor phases of a chemical substance
co-exist
Triple point is a point in a graph between
temperature and pressure at which three phases
like solid, liquid and vapours may co exist.
 z
Method of sublimation
The pressure below the triple point is called as
Sublimation pressure.
In the diagram the line (AO) is known as sublimation
pressure. At this (O) point solid and liquid are at
equilibrium. If the sublimation pressure is below this
triple point the solid will directly converted into vapor
phase and the vapor phase is directly change into solid.
Two factors in the diagram indicate that:
When the vapor pressure of the substance is less then
that of sublimation pressure, it will directly change into
solid or vapor phase without changing into liquid phase.
 Method of sublimation
z

When the vapor pressure of the substance is high

then that of the sublimation pressure, then it will first
convert into liquid phase and then into solid state on
further cooling.
The common sublimed substances are as follows:
Iodine
Naphthaline
Camphor
Para-dichloride benzene
Thus the vapor pressure of Iodine, camphor,
Naphthaline and p-dichloride benzene are less triple
point.
 z
Method of sublimation

In laboratory it consists of a china dish, a perforated

filter paper, funnel, and a cotton plug.
The material to be sublimed is placed in the china
dish; the china dish is covered with a perforated filter
paper. A glass funnel is placed in the inverted
position over the filter paper; the open end of the
funnel is plugged with cotton to prevent the escape
of sublimed product.
The china dish is heated and vapors pass through
the perforations of the filter paper, and are collected
on the inner surface of the glass funnel which is kept
cool from out side by wrapping a wet filter paper or
cotton wool. The vapors on cooling are condensed
into solid which is collected.
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APPLICATIONS
This process is used in the purification of many pharmaceutical
substances such as iodine, camphor, naphthalene, benzoic acid,
mercuric chloride, ammonium chloride.
This process is also employed to purify volatile solids contaminated
with non volatile impurities.
 Lyophilization /freeze drying
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Freeze drying is the process of drying in which water is sublimed from

the product after it is frozen.

Process: The freeze drying process is simple but more complicated as

follows:
During the process the temperature must be less below the triple point
in range of -10C to -30C. Similarly the process must also be kept
below the triple point. (4.6mmHg)
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 Lyophilization /freeze drying
z
The substance or solution is kept in a drying chamber.
The NH3 and Freon gases are used as refrigerants in the
chambers from the compressor through a pipe.
The chamber and condenser are then evacuated by the vacuum
pump.
The heat is then introduced by electric resistant coil or by
circulating hot water.
The process continues until the product is dried.
The provision of heat is controlled to avoid dissociation of the
substance.
The vapor produced in the chamber must be removed
continuously to avoid pressure rise, which would stop
sublimation.
So vapors are continuously removed by pumping. This process
is very prolonged and may take several hours for completion.
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Lyophilization or freeze drying
Application:
Liophilization is applied to prepare many biological
substances e.g.
blood plasma,
vitamins,
hormones,
enzymes,
vaccines,
antibodies.
Freeze drying process is used to dry freeze and to preserve
the biological substances and for the preservation of
different types of food product.
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Advantages:
Following are the some advantages of this
phenomenon,
Freeze drying take place at very low temperature, so
the decomposition of the substance is minimized.
The biological and pharmaceutical substances
which are unstable in aqueous solution are stored
in dry state. Freeze drying products are light and
porous and are usually readily soluble.
The product which are degraded or dissociated by
oxidation can be freeze dried, without dissociation.
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Disadvantages

Following are the three main disadvantages of this phenomenon:

1. The product becomes hydroscopic and dried and can be easily
dissolved. (porous product)
2. The process is very slow and much more time is wasted.
3. This process is very expensive and therefore is restricted to certain
types of valuable products that cannot be dried by any other process.
 Spray Drying
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Spray drying is one of the methods of desiccation by
which solutions or slurries are dried. The apparatus
used for this purpose is known as spray drier. These
driers consist of a hot air chamber into which liquid to be
dried is fed from the top and hot air is supplied from the
base. The spraying of the liquid is done either by
pressure jets .By the high current of hot air the liquid is
sprayed in the form of a mist, the droplets of which are
readily evaporated and the dried particles fall to the
bottom of the chamber from where they are collected.
The exhausted air leaves the chamber through the air
outlet.
Different types of spray driers are available with various
modifications. In some forms of spray driers the liquid to
be dried and hot air enters from the top of the chamber
and in others from the bottom. Still in other types liquid
is fed from the top and hot air from the bottom.
 Applications
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1. These driers are very useful because the drying

is very rapid as large surface of liquid is exposed
to hot air and temperature required for drying is
also low. Therefore heat sensitive products can be
dried conveniently.
2. Spray drying is used for drying blood plasma,
milk and enzyme preparations such as pancreatin
and pepsin.
3. Spray driers can be designed for drying under
sterile conditions.
4. Solid and liquid particles can be encapsulated
by employing pray drying.
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Trituration
By triturating the grinding of a solid substances is done
to fine powder by continuous strike in or rubbing the
particles in a mortar with a pestle. The term trituration is
also emloyed to designed the process by which two or
more powders are intimately mixed with each other. For
this purpose a pestle and mortar made of, porcelain or
glass is used. For hard materials steel mortar and pestle
may be used.

Trituration may be carried out with an ointment tile and

spatula or using a mortar and pestle.
 z Trituration using tile and spatula

Small quantities of finely powdered solids may be mixed on a

tile by means of a spatula.
Tiles are usually made of glass and should be large enough for
the quantity of powder to be mixed or ointment to be prepared.
Usually for small scale work 300mm square is a useful size for
a tile.
Spatula is made of stainless steel except for the few
medicaments those react with stainless steel (iodine), should
be flexible and long blade (25mm by200mm) to provide a large
rubbing surface.
Powders for Trituration are placed on the tile and gently mixed
until the mixture is smooth and homogeneous, but in the case
of ointment if base is very soft it may be helpful to warm the tile
but overheating should be avoided because the base will
become too fluid and may run off the edge of the tile. The
dispersion is then diluted with increasing amount of base,
doubling the quantity each on the tile of each dilution. Finally
 z Trituration using mortar & pestle

A mortar should be used when the quantities are too large .

A mortar with a fairly flat base and a pestle with a flat head
will give best results.
It is impossible to ensure intimate dispersion of one powder
in another by mixing the two substances all at once.
The purpose is to add a substance that is present in greater
amount to the whole of the substance present in lesser
amount. Substance present in greater amount is introduced
into the mixture in very small quantities at first, but gradually
increasing the quantities, until the whole of the substance
has been added..
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Levigation

The process of levigations is also known as wet grinding. In this

method the particle size of a substance is reduced to fine state of
subdivision by triturating the substance with a few drops of liquids to
which it is insoluble, in a glass mortar with the pestle or on a slab
with spatula .The most commonly used levigating agents includes
are oils, water, alcohols and glycerin.
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Pulverization by Intervention
This is a process by which the solid substances are reduced to a fine
powder by mean of trituration the solid using suitable solvent which can bee
easily removed by the end of process.
Camphor is triturated with few drop of alcohols, ether or chloroform it can be
powdered easily. The solvent added evaporate quickly leaving behind fine
sub-divided particles of camphor.
Similarly iodine crystals may be powdered with the help of small quantiy of
ether.