Described thoroughly about suspension.

1. PreparedBy:
Lecturer: Mr. S. S. Mistree
M-pharm(P’ceutics)
Sub: Pharmaceutics-II
Ishwar DeshmukhInstituteof Pharmacy, Digras
Yavatmal-445302
2020-21
BIPHASIC LIQUID DOSAGE FORM-
SUSPENSIONS

2. CONTENTS
Introductions
Classification of suspensions
Difference between flocculated and non-flocculated
suspension
Formulation of suspensions
Method of dispensing of suspensions
Stability of suspensions
Reference

4. INTRODUCTIONS
 Define: Suspension is a biphasic liquid dosage form, contain very fine
particles of insoluble solid material ( 0.5 to 5.0 micron) which are
dispersed in liquid or semi-liquid vehicle.
 This dosage form is made up of by two phase i.e. dispersed phase and
continuous phase.
 Dispersed phase- means solid particles of suspension
 Continuous phase- liquid vehicle of suspension
 Generally, suspension taken either orally, parentrally or instilled into
eyes. Also used for external applications.
 The particle size of solid substance plays an important role in
formulation of suspension.
 Externally applied suspensions particles should have small/fine
particles, which help to avoid gritty feeling to the skin and cover
greater area of application along with its help penetration of solid

5. medicament into skin, Because its smaller particle size gives a faster rate
of dissolution.
 Suspension for parenteral administration should have fine particles in
order to easily pass through the needle.
 Eye suspension should free from gritty particles, to avoid irritation
pain and discomfort.
 The particle size of suspended medicines should not go beyond 10
micron.
 Good qualities of suspension:
 It should settle slowly, readily re-dispersed on shaking.
 It should pour readily from its container.
 It should be chemically inert.
 The suspended/ dispersed particle should not form cake.
 It should be free from large particles, in order to avoid irritation to
sensitive tissues or spoil its appearance.

6. CLASSIFICATION
Suspension are classify in four main class on the basis of their
pharmaceutical use.
 Oral suspensions
 Parenteral suspension
 Ophthalmic suspension
 Suspension for external use.
1. Oral suspension:
 These kind of suspension are taken by oral route.
 It contain flavoring and sweetening agent in order to mask the bitter or
saline taste of drug.
 Also some time these bitter drugs given in derivative form to mask the
taste.
Eg- chloramphenicol= chloramphenicol palmitate

7.  Nowadays, oral suspension has been formulating in dry form, before
taken it need to reconstitute with purified water.
Eg: Antibiotic in suspension form for pediatric use.
 Advantages:
 Can easily swallowed the suspended insoluble drugs.
 Insoluble derivatives in suspension are more tasteful than soluble
derivative in solution.
 The bulky insoluble powder ( kaolin, chalk ) can be taken in
suspension in order to act as adsorbent of toxins or to reduce excess
acidity in the GIT .
 Disadvantages:
 It need to be shaken before measuring a dose.
 The accuracy of dose is less reliable than solution.
 On storage, chances of change in disperse system due to change in
temperature.

8. 2. Parenteral suspension:
 The suspension which are taken by parenteral route called as
parenteral suspension.
 Need to fulfill following qualities:
 Particle size should less in order to it can easily pass through needle.
 No crystal growth occurred in suspension during storage.
 The concentration of solid particles should be between 0.5 to 30%
 The viscosity of suspension should not interfere with its flow through
needle.
 It should be sterilized.
3. Ophthalmic suspension:
 Generally it is not popular as like eye drops, its rarely used.
 It formulate when drug insoluble in desire solvent or unstable in liquid
form.

9.  It must fulfill following condition:
 Its particle size should less, so that it should not cause any irritation to
eye.
 It should be sterile
 It should be isotonic
 It have desire viscosity.
 It should be packed in suitable container, so that it can be installed
easily into eyes.
4. Suspension for external use:
 These type of preparation are prepared for external application ( lotion,
inhalation, ear drop).
 Its particle size is very less to avoid grittiness.
 In lotion, suspended particles evaporate after application on skin and
leaving light deposit of drugs on the skin surface.
 Lotion is easy to apply and less messy than other semi-solid external
product.

10. Eg: calamine lotion.
 Lotion which are applied on broken or inflamed skin should be sterile.
 FLOCCULATED AND NON-FLOCCULATED SUSPENSION:
 Can said it flocculated suspension- when the individual particles are in
contact with each other and form a network like structure.
 Non-flocculated- when the individual particles exist as a separate
entity.
 We can discriminate suspension by following way.

11. FLOCCULATED
SUSPENSION
NON-FLOCCULATED
SUSPENSION
 Particles form network like
structure.
 Sedimentation rate is high.
 Sediment rapidly formed.
 Sediment easily redisperse
 Sediment is loosely packed
and not form cake.
 It has clear liquid.
 Floccules stick to side wall of
the bottle.
 Suspension has no pleasant
appearance.
 Particles exist in separate entity
( no network structure)
 Sedimentation rate is slow.
 Sediment slowly formed.
 Sediment difficult to redisperse
 Sediment closely packed and
form hard cake.
 It has no clear liquid.
 Floccules does not stick to side
wall of the bottle.
 Suspension has pleasant
appearance.

14. FORMULATION OF
SUSPENSION
Following additives are used for preparation of all kind of suspension.
 Flocculating agents
 Thickening agents
 Wetting agents
 Preservatives
 Organoleptic additives
1.Flocculating agent:
 In suspension, the fine solid particles should be thoroughly
distributed/suspended/dispersed into liquid vehicle(dispersion
medium)
 This dispersion we can improved by adding surfactant, which is act as
flocculating agent.

15.  These agents are reduce the surface tension of particles along with
improve the dispersion of solid particles and minimize the
flocculation.
Eg: SLS, carbowaxes , tweens , etc.
2. Thickening agent:
 This agent added to maintain desire viscosity in suspension.
 These agents are hydrophilic colloid which form a colloidal
dispersion with water and increase viscosity of dispersion medium.
 Due to viscosity solid particles remain in medium for sufficient time
and help to get accurate dose.
 Thickening agent are classified into three main groups-
• Polysaccharide
• Inorganic agent
• Synthetic compound

16. 2.1. Polysaccharides:
 Nowadays two types of polysaccharides used.
 Natural polysaccharide
 Semi-synthetic polysaccharide
2.1.1. Natural polysaccharide:
Eg: Gum acacia, tragacanth, starch, sodium alginate
i) Gum acacia:
 It is a good suspending agent and it is suitable for mixture containing
resin.
 It is more effective in compound tragacanth powder form.( 20%
acacia, 15% tragacanth, 20% starch and sucrose)
 This comp. tragacanth powder is employed in the concentration of 2
gm/ 100ml of mixture.
 When water and chloroform water not used as vehicle, then also comp.
tragacanth powder is used.

17.  Actually, gum acacia contains enzyme oxidase which casue
deterioration of easily oxidisable medicament.
 Hence, need to add benzoic acid and parahydroxy benzoic acid
(antimicrobial agent) to preserve the suspension containing gum
acacia.
ii) Tragacanth:
 It is a one of the popular thickening agent than gum acacia.
 It is available in two form i.e. comp. tragacanth powder (CTP) and
tragacanth mucilage (TM).
 The TM used to suspend heavy insoluble substance and when the
vehicle is water or chloroform water.
 Whereas CTP used, when vehicle is non-water or non-chloroform
water.
 Concentration of 1/4th of volume of mixture should be incorporate.
iii) Starch:
 It is rarely used with other suspending agent, bcz high viscosity of its
mucilage.

18.  Actually, it is a one ingredient of tragacanth powder.
vi) Sodium alginate:
 When dissolve in water it form a viscous solution.
 Its 1% solution has same power as tragacanth mucilage.
2.1.2. Semi-synthetic polysaccharide:
 Some cellulose are used as thickening agent:
• Methyl cellulose
• Sodium carboxymethyl cellulose
• Microcrystalline cellulose
i) Methyl cellulose:
 Its used as thickening agent with concentration 0.5 to 2 % for both
external and internal preparation.
ii) Sod. carboxymethyl cellulose:
 It is used with concentration from 0.25 to 1% for preparation meant for
oral, external and parenteral use.

19. iii) Microcrystalline cellulose:
 It is obtain from wood cellulose by acid hydrolysis.
 It is dispersible in water to produce colloidal dispersion.
2.2. Inorganic agents:
Eg: Clay and Aluminum hydroxide
i) Clay:
Eg: Bentonite and Aluminium magnesium silicate are used as thickening
agent.
 Bentonite is very pale buff of creamy hygroscopic powder.
 Its 2% suspension is used as suspending in-diffusible solid in
external preparation. Eg- calamine lotion.
 Aluminium magnesium silicate is creamy, colorless, tasteless
powder, used for external and internal preparation.

20. ii) Aluminium hydroxide:
 It act as suspending agent, when suspension contain barium sulphate,
calamine, sulphonamide and sulphur.
2.3. Synthetic compound:
Eg: Carbomer (carboxy vinyl polymer), colloidal silicon dioxide
i) Carbomer:
 It is used as thickening agent with concentration of 0.1 to 0.4 % for
internal and external preparation.
ii) Colloidal silicon dioxide:
 It is a white, non-gritty powder act as suspending agent with
concentration of 1.5 to 4%.
3. Wetting agent:
 The agent which minimize the interfacial tension between solid
particles and liquid medium and form a good quality of suspension.
Eg: alcohol in tragacanth mucilage, polysorbate in oral and parenteral
suspension.

21.  Avoid the excess use of it, may cause foaming or bad taste or odor to
the suspension.
4. Preservatives:
 It is very necessary to add preservative in suspension in order to
prevent the growth of bacteria, fungi or mould.
Eg: benzoic acid, sodium benzoate, methyl and propyl paraben
5. Organoleptic additives:
 In oral suspension generally coloring agent, sweetening and flavoring
agent are incorporated for improving its palatability.
 Whereas for external preparation, some perfume and color
incorporate.

22. METHOD OF DISPENSING OF
SUSPENSION
 Suspensions are categories into 4 type according to its method of
dispensing.
 Suspension containing diffusible solids
 Suspension containing in-diffusible solids
 Suspension containing precipitate forming liquids
 Suspension produced by chemical reaction
1. Suspension containing diffusible solids:
 The insoluble solids are light in weight and readily mix with water and
remain suspended throughout liquid after shaking for sufficient time
are called as diffusible solids.
Eg: calcium carbonate, light Mg. carbonate, rhubarb powder and light
kaolin.

23.  So, these kind of solid become difficult to dispense in liquid form,
hence it dispense as suspension form with following suitable methods.
 Method of dispensing:
1. Make a fine powder of all solid ingredients and weigh it as required
amount.
2. Mix the insoluble solid ingredient with some quantity of vehicle in
mortar and make smooth cream.
3. Add more vehicle to make it pourable.
4. Examine the suspension carefully.
5. If found any foreign particle, filter it with muslin cloth a tarred
container.
6. Rinse the mortal and pestle with vehicle and transfer it into container.
7. Add any liquid ingredients (if present)
8. Make a final required volume with vehicle and mix thoroughly by
shaking the bottle.

24. 2. Suspension containing in-diffusible solids:
 Those solid which are not soluble in water/vehicle and not remain
distributed in water/vehicle for sufficient time are called as in-
diffusible solids.
Eg: For external- calamine, zinc oxide, hydrocortisone
 For internal- aspirin, aromatic chalk powder, sulphadimidine
 Method of dispensing: ( using compound tragacanth powder)
1. Fine to all solid ingredients and weigh it
2. Mix all ingredient in mortar and add comp. tragacanth powder.
3. Measure 3/4th of vehicle and make a smooth cream.
4. Examine it carefully, if any particles visible, filter it with muslin cloth
into tarred bottle.
5. Rinse out mortar with vehicle and transfer it in bottle.
6. Add any liquid ingredients if present.
7. Make required volume with vehicle, cork it ,label it and dispensed it.

25. 3. Suspension containing precipitated forming liquid:
 There are many liquid preparation, on addition of it with water become
precipitated out.
Eg: Comp. benzoic tincture, Tolu tincture
 These liquid are not only insoluble but also form a in-diffusible ppt
when salts are present.
 The ppt produced due to it contain some resinous material and stick to
side wall of bottle its difficult to re-diffuse by shaking.
 So that to prevent this some protective colloids are used into it.
Eg: Compound tragacanth powder and tragacanth mucilage
 Method of dispensing:
o By using compound tragacanth powder:
1. In-diffusible and diffusible solids are fine into mortar and mix them
with compound tragacanth powder.
2. Add some amount of vehicle into mortar and triturate it until smooth
cream is formed.

26. 3. Measure the ppt forming liquid in dry M-cylinder and add it into
cream slowly with rapid stirring.
4. Dissolve soluble ingredients if present in sufficient vehicle add it
slowly into cream with constant stirring.
5. Examine it carefully, if any particles visible, filter it with muslin cloth
into bottle.
6. Rinse the mortal with vehicle and transfer into bottle.
7. Add any liquid ingredients
8. Make the final volume with adding more vehicle.
o By using tragacanth mucilage:
1. Tragacanth mucilage added when water or chloroform water are used
as vehicle.
2. Mix tragacanth mucilage with equal volume of vehicle in mortal.
3. Measure the ppt forming liquid in dry M-cylinder and add it slowly
in above mucilage with constant stirring.

27. 4. Dissolve any solid ingredients if present, in about 1/4th of vehicle and
mix with above mixture.
5. And follow the steps no-5, 6, 7, 8 from above procedure of using
compound tragacanth powder.
4. Suspension produced by chemical reaction:
 In this kind of suspension, the highly diluted solution of reactant are
mixed together to form very finely divided ppt that can easily
distributed throughout liquid by shaking.
 So we will get diffusible form suspension, hence there is no need to
add suspending agent
 Containers:
 Suspension should be packed in container having adequate air space
above the liquid to permit adequate shaking.
 Oral suspension should packed in wide mouth bottle to permit prompt
removal of suspension.

28.  Labeling:
 For liquid suspension, make a secondary label like “Shake well before
use”.
 For dry suspension powder- “Reconstitute it with given amount of
purified water”.
 Storage:
 It should be store in cool place but don’t keep in refrigerator.
 Avoid freezing otherwise it may cause aggregation of suspension

29. STABILITY OF SUSPENSIONS
 When suspension will redistribute uniformly with little shaking and
will easily pour from container up to its self life, then we called it
stable suspension.
 Most stable form of pharmaceutical suspension is flocculated, i.e. the
suspended particles are bonded together physically to from lose
structure, which is easily redistribute by little force.
 The non-flocculated suspensions can make stable by decreasing its
particle size of the suspended material or by increasing density and
viscosity of vehicle.
 Evaluation of the stability of suspension:
 For the testing of physical stability of suspension following methods
are employed.

30.  Sedimentation method
 Micromeritic method
 Rheological method
 Electro-kinetic method
1. Sedimentation method:
 The study of sedimentation volume of suspension is very important to
find out whether the given suspension is stable or not.
Steps:
 Put a measured volume of suspension in graduated cylinder in
unmovable position for specific time.
 After that note down the ultimate height and initial height of total
suspension.
 And the value put in given formula:
Hu
F= ----------------
Ho

31. Where,
Ho – is a initial height of suspension
Hu – is a ultimate height of suspension
F – is a sedimentation volume of suspension
 The F value can be plotted against time, a stable suspension will show
horizontal or less steep curve.
 The evaluation of redispersibility can also determine by shaking
suspension and again find out F value of suspension.
2. Micromeritic method:
 Actually, also the stability of suspension depend on particle size of
dispersed phase.
 With time, may change in size of particles may grow and lead to
formation of lump and cake.
 And that change in particle size and crystal habit may be studied by
microscopy or coulter counter method.

32. 3. Rheological method:
 The change in viscosity of suspension may responsible for affecting
the stability of it.
 So it is important to determine viscosity with the help of viscometer.
4. Electro-kinetic method:
 Also its become helpful to determine surface electric charge or zeta
potential of suspension, to understand that whether suspension is
stable or not.
 This zeta-potential are calculated by the electrophoric method.

33. REFERENCE
R. M. Mehta, pharmaceutics-II, second adition-2003,reprint 2010,vallabh
Prakashan. Pg. No. 123 to 135.