PREFORMATION CONCEPTS

Presented By

Praveen Kumar D

College of Pharmacy

Madras Medical college

M Pharmacy 1st year

(Pharmaceutics)

DRUG EXCIPIENT
INTERACTION

INTRODUCTION

❖ Excipients play an important role in formulating a dosage
form. These are ingredients which along with active
pharmaceutical ingredients make up the dosage forms.
Excipients act as protective agents, bulking agents and
can also be used to improve bioavailability of drug.

❖Excipients as like other active pharmaceutical ingredients
need to be stabilized and standardized .

EXCIPIENT

➢ An excipient is an inactive substance formulated alongside the active
ingredient of a medication, for the purpose of bulking-up formulations
that contain potent active ingredients .

➢ The resultant biological, chemical and physical properties of the drug
product are directly affected by the excipient chosen, their
concentration and interaction with the active pharmaceutical
ingredients.

➢ Consistency of drug release and bioavailability.

➢ Stability including protection from degradation.

➢ Ease of administration to the target patient populations by the intended
route

IDEAL PROPERTIES OF EXCIPIENT

❑No interaction with drug

❑Cost effective

❑Pharmacological inert

❑Stable for handling

❑EXCIPIENT ARE INACTIVE
INGREDIENTS USED AS CARRIER FOR
THE ACTIVE INGREDIENTS IN A
PHARMACEUTICAL PRODUCT.
THESE MAY BE CLASSIFIED INTO THE
FOLLOWING CATEGORIES

1. Anti adherents

2. Binders

3. Disintegrants

4. Preservatives

5. sweeteners

DRUG EXCIPIENT INTERACTION

IN PHARMACEUTICAL DOSAGE FORMS THE ACTIVE
PHARMACEUTICAL INGREDIENTS ARE INTIMATE
CONTACT WITH THE EXCIPIENT WHICH ARE GREATER
QUANTITY EXCIPIENT AND DRUGS MAY HAVE CERTAIN
INCOMPATIBILITY WHICH LEAD TO DRUG EXCIPIENT

INTERACTION.

TYPES OF DRUG EXCIPIENT INTERACTIONS

1.Physical interactions.
2.Chemical interactions.
3.Biopharmaceutical interactions.
4.Excipient — excipient interactions.

1.PHYSICAL INTERACTIONS

Physical interactions alter the rate of
dissolution, dosage uniformity, etc. Physical
interactions do not involve chemical
changes thus permitting the components in
the formulation to retain their molecular
structure. Physical interactions are difficult
to detect.

INTERACTION BENEFICAL EFFECT EXAMPLES DETRIMENTAL EFFECT
EXAMPLES

Complexation :- Cyclodextrin is often used to improve Tetracycline formed insoluble
Usually binds bioavailability of poorly water soluble complex with calcium
reversibly with drugs drugs. This increases bioavailability and carbonate leading to slower
to form complex, increases rate and extent of drug dissolution and decreased
sometimes insoluble dissolution by increasing mucosal and decreased absorption.
complexes are permeability or increasing stability of
formed which lead drug.
to slower dissolution
and decreased
absorption drug.

2. CHEMICAL INTERACTIONS

Active pharmaceutical ingredients and excipients react with each other to form
unstable compounds.

INTERACTION FACT OBSERVED EXAMPLE OF DRUG UNDERGOING SUCH
INTERACTIONS

Hydrolysis Drugs with functional groups like esters, Anesthetics , Antibiotics , Vitamins , and
amides, lactones, undergoes Barbiturates.
hydrolysis, in presence of water, low or
high pH, in presence of alkaline
metals, acids i.e. anion and hydrogen
ion, alkali etc.

Oxidation Oxidative reactions are catalyzed by Steroids Vitamins , Antibiotics , Epinephrine ,
oxygen , light , heavy metal ions, Aldehydes , Alcohols , Phenols.
fumed metal oxides , fumed silica ,
fumed , zirconia etc.

3. BIOPHARMACEUTICAL INTERACTIONS
These are the interaction observed

after administration of the
medication. Interaction within the
body is between medicine and body
fluids which influence the rate of
absorption. All excipient
physiological way when they are
administered along with active
pharmaceutical ingredients.

EXAMPLES
1. PREMATURE BREAKDOWN OF ENTERIC COAT

The enteric coating polymers like cellulose acetate
phthalate and hydroxyl propyl cellulose acetate phthalate.
Are soluble more at basic pH , antacids raise pH of stomach
resulting in breakdown of the enteric coat in stomach and
release of active pharmaceutical ingredient in stomach itself ,
which result in degradation of drug in stomach . In case of
NSAID’ s premature breakdown of enteric coat many cause
side effects like gastric bleeding.

2. INCREASE IN GASTROINTINAL MOTILITY

Many of the excipients like sorbitol , xylitol have
tendency to increase the gastrointestinal motility thus
reducing the time available for absorption of drugs like
metoprolol.

4. EXCIPIENT – EXCIPIENT INTERACTIONS.

Excipient – excipient interaction though
observed very rarely. These are prime importance
in determining the stability of the dosage forms
excipient – excipient interactions can be
undesirable as well as some interactions are used
in the formulations to get the desired product
attributes.

KINETIC OF STABILITY
&

STABILITY TESTING



CONTENTS
1.Definition of drug kinetics
2.Importance of studying kinetics
3.Rate and order of reaction
4.Factors affecting rate of reaction
5.Kinetics of drug degradation
6.Stability testing
7.Scope of stability testing
8.Advantage of stability testing
9.Types of stability
10.Stability testing methods
11.Guidelines for stability testing
12.Climatic zone for stability testing
13.Estimation of shelf life
14.Expiration date

❖ DRUG KINETICS
Defined as how drug change with time
i.e. study of rate of change.

Many drugs are not chemically stable
and the principle of chemical kinetics are
used to predict the time span for which a
drug will maintain its therapeutic
effectiveness or efficacy at a specified
temperature

IMPORTANCE OF STUDING KINETICS
It determine:

➢Stability of drug / half life of drug defined as time
necessary for a drug to decay to its half or 50%
conc.

➢ Shelf life- defined as the time required for a drug to
decay to 90% of its original conc.

RATE AND ORDER OF REACTION
➢ The velocity with which a reaction or process occurs is called its rate.
➢ The cone. Of drug which influences the rate of reaction or process is called its order of

reaction.
Consider the following chemical reaction

DRUG A DRUG B

➢ The rate of forward reaction is expressed by-

– dA/dt

➢ As the reaction proceeds , the conc. Of drug B increases & rate of reaction can be
expressed by-

dB/dt

o If C is the conc. of drug A as it is changed to B can be described by expression as a
function of time t;

dC/dt = – KCn

Where
K = rate constant

n = order of reaction

if , n = 0 (Zero order kinetics )
n = 1 (first order kinetics )

The two commonly encountered rate processes are:

1.ZERO ORDER REACTION
2.FIRST ORDER REACTION

ZERO ORDER REACTION

✓ Also called as constants rate process.
✓ The rate of reaction is independent of conc. i.e rate of reaction cannot be increased

further by increasing the conc. Of reactant.

dC/dt = – 𝐾0𝐶0 = – 𝐾 ………………… 𝑒𝑞𝑛1
0

Where, 𝐾0 = 𝑧𝑒𝑟𝑜 𝑜𝑟𝑑𝑒𝑟 𝑟𝑎𝑡𝑒 𝑐𝑜𝑛𝑠𝑡𝑎𝑛𝑡𝑠 (𝑖𝑛 mg/ min)
Rearranging 𝑒𝑞𝑛 1:

dC = – 𝐾0 dt ………………. 𝑒𝑞𝑛2

Integrating the 𝑒𝑞𝑛 2:
𝑐 𝑡

න 𝑑𝑐 = න −𝑘𝑜𝑑𝑡
𝑐𝑜 0

C – 𝐶0 = – 𝐾0𝑡

Where ,
𝐶0= conc. Of drug at t = 0
C = conc. Of drug yet to undergo reaction at time t

𝐶0

Slope = -𝐾0

dC/dt Type equation here. C

Time (t) Time (t)

Graph of zero order kinetics showing relationship b/w
Rate of reacting and conc. Of drug

FIRST OREDER REACTION

❖ These are the reaction whose rate is directly proportional to conc. Of the drug
undergoing i.e. greater the conc., faster the reaction.

❖ It follows linear kinetics.
dC/dt = – KC ……………………𝑒𝑞𝑛 3

Where, K = first order rate constant (per hour)
Rearranging the above 𝑒𝑞𝑛 3,

……………………𝑒𝑞𝑛 4
dC/C = – Kdt

Integrating the above𝑒𝑞𝑛 4,

𝐶 𝑡
׬ 𝑑𝐶/𝐶=
𝐶 ׬ = −𝐾𝑑𝑡
0 0

In C- In 𝐶0= – Kt
In C = In 𝐶0- Kt

In terms of log.

Iog C = log 𝐶0 – Kt/2.303

Slope = – K/2.303

Log C

Time (t)

Graph of first order kinetics showing linear relationship b/w rate of reaction and concentration. of drug

Factors affecting rate of reaction

1.Temperature
2.Light
3.Solvent
4.Phase & Surface Area
5.Catalysis
6.Concentration

KINETIC OF DRUG DECOMPOSITION

The drug decomposition follows the degradation pathway-

❖Hydrolysis
❖Oxidation
❖Photolysis
❖Racemization

HYDROLYSIS
❑Many pharmaceuticals ester or amide hydrolysis of an

ester hydrolysis in solution. E. g. anesthetics, antibiotics, vitamins, & barbiturates.
❑ The hydrolysis of an ester in acid & alcohol rupture of a covalent

linkage b/w Carbon & oxygen atom. e.g. Aspirin.
❑ The hydrolysis of amide gives acid & amine. E.g. barbiturates,

chloramphenicol.

Prevention
❖ pH
❖ Type of solvent (ethanol, mannitol)
❖ Reduction to salts.

OXIDATION

❖The oxidative decomposition instability of
preparation such as steroids, vitamins, antibiotic &
epinephrine.

❖Reaction mediated either by free radicals or by molecular
oxygen.

❖Autoxidation involves a free radical chain process.

AB A* + B
❖These radicals are highly unstable & readily take electrons

from other substances, causing oxidation

FUNCTIONAL GROUP SUSCEPTIBLE TO OXIDATION

Functional Group Drugs/Excipients

Aldehydes Paraldehyde

Amines Clozapine

Carboxylic acids Fatty acids

Conjugated dienes Vitamin A

Ethers Diethyl ether

Nitrites Amyl nitrite

Phenols Catecholamine, Morphine

Prevention:
❑ Low oxygen content
❑ Antioxidants
❑ PH

PHOTOLYSIS

✓Photolytic degradation exposure to UV or visible light in
the wavelength range of approx. 300-800 nm.

✓Photo degradation rates directly dependent on the
amount of incident radiation & on the amount of radiation that is
absorbed by the compound.

✓Alcoholic solutions of hydrocortisone, prednisolone, &
methylprednisolone degrade by

photolytic reactions following first – order kinetics.

RACEMIZATION

❑An optically active substance loses its optical activity
without changing its chemical composition.

❑Dextro form generally therapeutically less active that Ievo
from. E.g. Ievo of adrenaline is 20 times active than dextro.

STABILITY TESTING

Stability : defined as capability of a particular formulation in
specific Container/closure system to remain within its physical,

1 chemical, microbiological, toxicological, protective and
informal specifications.

It is the extent to which a product retains, within the specified

2 limits, throughout its period of storage and use, the same
properties and characteristics possessed at the time of its
packaging.

SCOPE OF STABILITY TESTING

➢Provide as to how the quality of drug product
varies with time.
➢Establish shelf life of drug product.
➢Determine recommended storage conditions.
➢Determine container closure system suitability.

IMPORTANCE OF STABILITY TESTING

❖Assurance to patient that drug is safe.
❖Legal requirement to provide data.
❖To protect the reputation of the manufacture.
❖To provide a database.
❖To determine shelf life and storage conditions.
❖To verify that no changes have been introduced in

the formulation or manufacturing process that can
adversely affect the stability of the product.

TYPE OF STABILITY

o Each active ingredient retain its chemical integrity and labeled
Chemical

potency within specified limits.

o Includes appearance, palatability, uniformity, dissolution and
Physical

suspend ability are retained.

o Sterility or resistance to microbial growth is retained according to
Microbiological

specific requirement.

Therapeutic o Activity remains unchanged.

Toxicological o No significant increase in toxicity

STABILITY TESTING METHODS

1. REAL TIME STABILITY TESTING
2. ACCELERAYED STABILITY TESTING
3. RETAINED SAMPLE STABILITY TESTING
4. CYCLIC TEMPERATURE STRESS TESTING

1. REAL TIME STABILITY TESTING

❖Performed for longer duration of the test period in order to all
significant product degradation under recommended
storage conditions.

❖Depends upon the stability of the product which should be
long enough to indicate clearly that no measurable
degradation occurs.

Stability of reference
Date collected at To distinguish

material include the
appropriate Instability from

stability of reagent as well
frequency day to day

as consistency of
performance

2. ACCELERATED STABILITY TESTING

❖ A product is stressed at several high temp. & the amount of heat input

required to cause product failure is determined.

❖ This is done to subject the product to a condition that accelerates

degradation.

❖ This information is then projected to predicted to predict shelf life or

used to compare the relative stability of alternative formulations.

Samples subjected to Assayed
Refrigerated

stress Simultaneously

The concept of accelerated stability testing is based upon the Arrhenius
equation

Δ𝐸
In K = In A +

RT

Where,

K = degradation rate/s,
A = frequency factor/s,
E = activation energy (kJ/mo1),
R = universal gas constant (0.00831 kJ/mo1),
T = absolute temperature (K)

3.RETAINED SAMPLE STABILITY TESTING

❑ Usual practice for every marketed product for which stability data

are required.

❑ Only one batch a year are selected.

❑ If the number of batches marketed exceeds 50, stability sample from two batches are

recommended to be taken.

❑ Stability testing by evaluation of market samples is a modified method which involves

taking samples already in the market place and evaluating stability attributes

4. CYCLIC TEMPERATURE STRESS TESTING

➢ Is not a routine testing method for marketed products

➢ In this method, cyclic temp. stress tests are designed on knowledge of the product so as

to mimic likely condition in market place storage.

➢The period of cycle mostly considered is 24 hours.

➢The min. and max. temp. for the cyclic stress testing is recommended to be selected on

a product by – product basis and considering factors like recommended storage temp.

for the product and specific chemical and physical degradation properties of the

products.

➢The test should normally have 20 cycles.

GUIDELINE FOR STABILITY TESTING

ICH CODE GUIDELINE TITLE

QIA Stability testing of New Drug Substances and Products
(Second Revision)

QIB Stability testing : Photo stability testing of New Drug
Substances and Products

QIC Stability testing of New Dosage Form

QID Bracketing and Matrixing Designs for stability testing of drug
substances and Products

QIE Evaluation of stability data

QIF Stability data package for Registration Applications in
Climatic Zones III and IV

Q5C Stability testing of Biotechnological/Biological Products

CLIMATIC ZONES FOR STABILITY TESTING
Zone II

Zone I Zone III Zone IV
(SUBTROPICAL &

(TEMPERATE) (HOT & DRY) (HOT & HUMID)
MEDITERRANEAN)

❖ United ❖ Japan, Southern
❖ Iraq, India. ❖ Iran, Egypt.

Kingdom, Europe.
❖ Long term

Northern ❖ Long term testing
❖ Long term testing

Europe, condition- testing conditions-
conditions- 30°∁/𝟔𝟓%𝑹𝑯

Russia 25°∁/𝟔𝟎%𝑹𝑯
30°∁ %𝑹𝑯

𝟑𝟓
United states.

❖ Long term

testing

conditions-

❖ 21°∁/𝟒𝟓%𝑹𝑯

Test storage condition
Intended storage Study Storage condition Minimum time
condition Period covered

Room temperature Long term 25°∁ ± 2°∁/60%𝑅𝐻 ± 5% 𝑅𝐻 12 Months

Intermediate 30°∁ ± 2°∁/65%𝑅𝐻 %± 5% 𝑅𝐻 6 Months

Accelerated 40°∁ ± 2°∁/75%𝑅𝐻 ± 5% 𝑅𝐻 6 Months

Long 5°∁ ± 3°∁ 12 Months

Refrigerated Accelerated 25°∁ ± 2°∁ 60% 𝑅𝐻 ± 5% 𝑅𝐻 6 Months

Freezer Long -20°∁ ± 5°∁ 12 Months

ESTIMATION OF SHELF LIFE

➢The time period during which a drug product is expected to

remain within the approved shelf life specification, provide that it

is stored under the conditions.

➢The time period during which the drug maintain its 90% potency

or loss not more than 10 % potency.

➢The shelf life is determined from the data obtained from the data

obtained from the long term storage studies.

EXPIRATION OF DATA

➢ An expiration data is defined as the time up to which the product will

remain stable when stored under recommended storage conditions.

➢ Thus, an expiration data is the date beyond which it is predicted that the

product may no longer retain fitness for use.

➢ If the product is not stored in accordance with the manufacture’s

instructions, then the product many be expected to degrade more

rapidly.

THEORIES OF DISPERSION AND
PHARMACEUTICAL
DISPERSION

CONTENTS:

❑Emulsion Definition
1. Theories of Emulsification
2. Method of preparation of Emulsion
3. Instability of Emulsion

❑Suspension Definition
1. Method of preparation of Suspension
2. Preparation techniques for suspension
3. Stability of suspension

EMULSION:

❖A thermodynamically unstable system consisting of at least 2

immiscible liquid phases, 1 of which is dispersed as globules in the

other liquid phase.

❖The dispersed liquid is known as the internal or discontinuous

phase.

❖Where as the dispersed medium is known as the external or

continuous phase.

Theories of Emulsification:

❖ Many theories have been advances to account for the way or means by which the
emulsion is stabilized by the emulsifier.

1. Electric double layer Theory.
2. Phase Volume Theory.
3. Hydration Theory of Emulsions.
4. Oriented wedge theory.
5. Adsorbed Film and Interfacial tension Theory.

1. ELECTRIC DOUBLE LAYER THEORY

➢ Layer of oppositely charged ions forms a layer in the oil globules in
a pure oil and pure water emulsion carry a negative charged. The
water ionizes so that both hydrogen and hydroxyl ions are present.

➢ The negative charge on the oil may come from adsorption of the
OH ions.

➢ These adsorbed hydroxyl ions form a layer around the oil globules.
A second liquid outside the layer of negative ions

➢ The electric charge is factor is a factor in all emulsions, even those
stabilized with emulsifying agents.

2. PHASE VOLUME THEORY:

✓ If spheres of same diameter are packed as closely as possible,
one sphere will touch 12 others and the volume the spheres
occupy is about 74 per cent of the total volume.

✓ Thus if the spheres or drops of the dispersed phase remain rigid it is
possible to disperse 74 parts of the dispersed phase in the
continuous phases; but if the dispersed phase is increased to more
than 74 parts of the total volume, a reversal of the emulsion will
occur.

✓However, the dispersed phase does not remain rigid in shape but
the drops flatten out where they come in contact with each other,
nor are all the dispersed particles the same.

3. HYDRATION THEORY OF EMULSIONS:

➢ Fischer and hooker state that hydrated colloids make the best
emulsifiers.

➢Fischer states the emulsifying agent, by which a permanent
emulsion is obtained, ‘ proves to be a hydrophilic colloid when
water and oil emulsions are concerned.

➢Fischer and hooker have found albumin, casein, and gelatin to be
good emulsifying agents.

4. ORIENTED WEDGE THEORY:

▪ This theory deals with formation of monomolecular layers of emulsifying
agent curved around a droplet of the internal phase of the emulsion.

EXAMPLE:

▪ In a system containing 2 immiscible liquids, emulsifying agent would be
preferentially soluble in one of the phases and would be embedded in
that phase.

▪ Hence an emulsifying agent having a greater hydrophilic character will
promote o/w emulsion and vice – versa.

▪ Sodium Oleate is dispersed in water and not oil. It forms a film which is
wetted by water than by oil. This leads the film to curve so that it
encloses globules of oil in water.

5.ADSORBED FILM & INTERFACIAL TENSION THERORY:

✓ Lowering interfacial tension is one way to decrease the free surface
energy associated with the formation off droplets. Assuming the droplets
spherical,

∆F = 6 𝜸 𝑽Τ𝑫
✓ Where,
✓ V = volume of the dispersed phase in ml,
✓ D = Mean diameter of the particles.
✓ Y = Interfacial tension
✓ It is desirable that the surface tension should be reduced below

10daynes / cm by the emulsifier and it should be absorbed quickly.

METHODS OF PREPARATION OF EMULSION;

❖Commercially, emulsions are prepared in large volume mixing tanks
and refined and stability by passage through colloid mill or
homogenizer.
Extemporaneous production is more concerned with small scale
methods.

METHODS:

1. dry Gum Method
2. wet Gum Method
3. Bottle Method
4. Beaker Method
5. In situ Soap Method

1. DRY GUM METHOD:
o Dry gum Method is used to prepare the initial or primary emulsion from

oil, water, and a hydrocolloid or “ gum “ type emulsifier.
o Dry Gum Methodology (4 parts oil, 2 parts water, and 1 part Emulsifier).

Procedure:
o Take mortar, 1 part gum is levigated with the 4 parts oil until the powers is

thoroughly wetted; then the 2 parts water are added all at once, and the
mixture is vigorously

triturated until the primary emulsion formed is cream white and
produces a “ cliking “ sound as it is triturated.

o Active ingredients, preservatives, colour, flavor’s are added as a solution to
the primary emulsion.

o When all agents have been incorporated, the emulsion should be transferred to
a calibrated vessel, brought to final volume with water.

2. Wet gum method

❑Methodology
❑(Oil 4 parts + water 2 Parts + emulsifier 1 parts)

Procedure

❑In this method, the proportions of oil, water and emulsifier are the
same (4:2;1), but the order and techniques of mixing are different.

❑The 1 part gum is triturated with 2 parts water to from a mucilage;
them the 4 parts oil is added slowly, in portions, while trituration.

❑After all the oil is added mixture is triturated for several minutes to
form the primary emulsion.

❑Then other ingredients may be added as in the continental method.

3. BOTTLE METHOD:

❖This method may be used to prepare emulsions of
volatile oils, Oleaginous substances of very low
viscosities.

❖This method is a variation of the dry gum method.
❖One part powdered acacia (or other gum ) is

placed in a dry bottle and four parts oil are added.
❖The bottle is capped and thoroughly shaken.
❖To this, the required volume of water is added all

at once, and the mixture is shaker thoroughly until
the primary emulsion forms.

4. BEAKER METHOD:

➢Dividing components into water soluble and oil soluble
components.

➢All oil soluble components are dissolved in the oily phase
in one beaker and all water soluble components are
dissolved in the water in separate beaker.

➢Oleaginous components are melted and both phases are
heated to approximately 70°𝑪 over a water bath.

➢The internal phase is then added to the external phase with
stirring until the product reaches room temperature.

5. IN SITU SOAP METHOD:

✓Two types of Soap developed by this Methods:
✓Calcium soaps
✓Soft Soaps
✓1) Calcium soap: W/O types emulsions
✓E.g. Oleic acid + Lime water. Prepared by simple

mixing of equal volumes f Oil and Lime water.
✓Emulsifying agent used is Calcium salt of free

fatty acids.
✓E. g. Olive oil + oleic acid (FAA)

INSTABILITY IN EMULSION:

Instability Factors Prevention

Flocculation: 1) Uniform globule size 1) Uniform sized globules.

Globules come closes each distribution. 2) Use same charged ionic

other to form aggregates. 2) Opposite charge on globule electrolytes.
surface. 3) Viscosity improving agents

3) Low viscosity of external hydrocolloids.
medium.

Creaming; 1. Globule size. 1.Homogenization uniformed
Concentration of globules at 2. Viscosity of external medium. size globules.
top/bottom of emulsion. 3. Differences in density of oil- 2. Thickening agents to.

water (aq >oil). improve viscosity
3. Reducing density differences

(Bromoform+oil).

Coalescence: 1. Insufficient amount of E.A NO this is permanent change
Few globules fuse to form bigger 2. Altered portioning of E.A
globules emulsifier film is 3. Incompatibility between E.A
destroyed. 4. Phase volume ration > than

74%

INSTABILITY FACTORS PREVENTION

Breaking: Unnoticed coalescence No this is permanents change
Complete separation of oil &
aqueous phases

Phase inversion: 1. Change in chemical nature
Change in emulsion from o/w of E.A → Sodium sterate
to w/o or vice versa (water soluble) →o/w

emulsion.
Sodium sterate + CaC𝐼2 →
calcium sterate
Calcium sterate (oil soluble) →
w/o emulsion.
1. Altering phase: volume

ration
o/w emulsion + oil → w/o
Emulsion should + water → o/w
this method should be properly
controlled other wise lead to
the phase inversion.

SUSPENSION:

❖A pharmaceutical suspension is a coarse dispersion in which internal
phase is dispersed uniformly through the external phase.

METHOD OF PREPARATION OF SUSPENSION:
Suspension can be prepared by 2 methods:
❖ Precipitation methods:
❖Dispersion method:
PRECIPITION METHODS:
Three main methods
❖Organic solvent precipitation
❖Precipitation effected by changing pH of the medium
❖Double decomposition

• ORGANIC SOLVENT PRECIPITION:

Water insoluble drug

Dissolve in organic solvents

Add organic phase to eater
organic solvents include ethanol,

Methanol, propylene glycol and
polyethylene glycol.

❑Precipitation effected by changing pH of the
medium:

Application to those drugs in which solubility is dependent on pH value.
Concentrated solution in favorable pH

Pour to other system to change pH

On agitation precipitate will form
e.g. estradiol suspension.

DOUBLE DECOMPOSITION:

➢ Two water soluble reagent forms a water
insoluble product.

➢E g white Lotion NF
Zinc sulphate solution

Solution of sulphureted potash

Precipitate of zinc polysulphide

DISPERSION METHOD:

Vehicle is formulated

Solid phase is wetted and dispersed

Use of surfactant to ensure wetting of hydrophobic
solids

PREPARATION TECHNIQUES OF SUSPENSION:

❖Small scale preparation of suspensions
❖Large scale preparation of suspensions

SMALL SCALE PREPARATION OF SUPENSION:

Grinding insoluble materials with vehicle containing the
wetting agent

↓

Soluble ingredients are dissolved in same portion of the vehicle

↓
Added to the smooth paste to step to get slurry.

↓
Make up the dispersion to the final volume.

LARGE SCALE PREPARATION OF SUSPENSION:

➢ If suspension is made by dispersion process it is best to achieve
pulverization of solid by micronization technique or spray drying

➢ If suspension is made by controlled crystallization, a
supersaturated solution should be formed and then quickly cooled
with rapid stirring.

STABILITY OF SUSPENSION:

1) Small particle size:
Reduce the size of the dispersed particle increase the total

surface area of the solid. The greater the degree the subdivision of
given solid the larger the surface area.

The increase in surface in surface area means also an liquids
leading to an increase in viscosity of a system.

2) Temperature:
Another factor which negatively affects the stability and

usefulness of pharmaceutical suspension is fluctuation of temp
Temperature fluctuations lead caking of claying.

3. INCREASING THE VISCOSITY

❖Increasing the viscosity of the continuous phase can lead to the
stability of suspension this is so because the rate of sedimentation
can be reduce by increase in viscosity.

❖Viscosity increase is brought about by addition of thickening
agents to the external phase. In water these must be either soluble
or swell.

❖It is important to note that the rate of release of drug from a
suspension is also dependent on viscosity of a product.

❖The more viscous the preparation, the slower Is likely to the
release of a sometimes this property may be desirable for depot
preparations.