1. Suspensions

2. Definition -A heterogeneous system in which the
continuous phase is a liquid or semisolid, and the
dispersed phase consists of a dispersed solid.
• Acceptable properties of a suspension:
1. Particles should not settle rapidly
2. When particles settle, should not form hard cake (i.e. be readily dispersible)
3. Product should be viscous enough so patient gets
uniform dose, but not so viscous to prevent pouring or injecting.

3. Pharmaceutical Suspensions
• Heterodisperse systems
• Particles often > 1 um (usually > 10 um)
• Complex continuous phase
– Viscosity Inducing agents, flavors, etc.
• Particle shapes non-spherical
• High solids content

4. Why Use Suspensions?
1.No suitable solvent available to dissolve drug (i.e. ZnO)
2. Mask unpleasant taste of drugs
– (i.e. chloramphenicol palmitate, Chloromycetin, Parke Davis )
– garlic-like taste for chloramphenicol
– palmitate salt masks taste ,
– also more stable in gastric juices so increased blood levels
– at pH 3-6, palmitate hydrolyzes
3. To increase chemical stability
– Ex. Penicillin G rapid hydrolysis in solution
– Procaine Penicillin G no hydrolysis if decrease solubility
below 1.5 mcg/ml. (G = glutamate)
4. To Control Therapeutic Response
– Insulin—Different Release Rate
– Depot Systems—Suspension Injections for time release

5. Properties well formulated suspension
suspension must be consist of small and uniformly sized particles. If the suspension is allowed to stand , the dispersed particle settle down gradually and ultimately two distinct phase are found after a certain period of time.
The particle which settle to the bottom of the container should not pack into hard cake .
The sediment particles must be re-dispersed easily on agitation.
The suspension should not be too viscous to pour freely from the orifice of the bottle.

6. The suspension must be homogenous until the period of time to take the required dose .
Viscosity must be controlled to reduce the rate of settling down of the particle.
The suspension should have pleasing odour, colour and taste.
The product should not support bacterial growth during storage .
It should be economically feasible..

7. Classification of suspension
Suspension can be classified into two ways :
According to the route of administration :
Oral suspension :
i) aqueous suspension. e.g. antacid suspension.
ii) non-aqueous suspension. e.g. Mandelate oral
suspension.
iii) Dry granules .e.g. amoxicillin suspension.
Injectable suspension. e.g. Penicillin injection.
Topical suspension. e.g. calamine lotion.
Ophthalmic suspension. e.g. chloramphenicol.
Aerosol suspension. e.g. dexamethasone phosphate suspension.

8. According to aggregation of particles :
a) Flocculated suspension :
The suspension in which the dispersed particles are settle down easily and return to it’s original phase on stirring without delay, is called flocculated suspension. The rate of settling down is depend on aggregation of particles.
b) Deflocculated suspension :
The suspension in which the dispersed particles are settle down and formed hard mass and by agitation do not return to the original phase easily, is called deflocculated suspension.

9. Stoke’s law :
Sedimentation rate is directly proportional to the radius of the particles and the density difference between the dispersed phase and dispersion medium and inversely proportional to the viscosity of the dispersion medium. Mathematically stoke’s law is expressed by the following equation :

10. Stoke’s Law •Most important law controlling formulation of suspensions
In equation:
V= 2r2 ( p – po) g / 9ŋ
V = rate of settling of the particles
r = radius of the particles
p = density of the particles
po= density of the medium
g = gravity constant
η = viscosity of the dispersion

11. – Stokes Law assumes:
• Particles are spherical
• Suspensions are dilute (<2% w/v)
• Particles do not flocculate
• No Brownian movement
• No electrical effects

12. Stoke’s Law Applications
• Pharmaceutically we can control suspensions by:
1.) Radius of the particles (r)
V α r2 (Decrease radius, then increase SA and
increase surface energy)
-a high surface energy leads to aggregate formation,
so use a peptizing agent (Na+ citrate in calamine
lotion) to place surface charge on the particles so
they do not aggregate, and the surface charge repels the particles
- aggregates form to reduce (minimize) surface energy.

13. 2.) Viscosity (η) of the medium—Suspending Agents
--Rate of settling is inversely proportional to viscosity
Examples of suspending agents:
-acacia, tragacanth – In, too sticky for Ex
-Carboxymethylcellulose (CMC) –In or Ex
-Veegum (montmorrilonite clays) -use hydrated, In
or Ex
-Carbopol -a gum, use in pH range 5-10, In or Ex
--Viscosity inducing agents -swell in water to increaseviscosity

14. Limitation of stoke’s Law :
Formulation containing 2gm|100ml follow this equation. But above 2gm|100ml , the law is invalid.
It is not acceptable for concentrated suspension.
According to this equation particles should be rigid , spherical and uniform in size. But in practical the particles are not totally uniform.

15. Methods of Preparation of Suspensions
Dispersion Method -add dispersion medium to finely
divided particles
1. Diffusible powders—no suspending agent required, will
remain suspended long enough for uniform dose
Ex: Kaolin, Mg Carbonate, Mg Oxide, Quinine sulfate and
Bismuth subcarbonate—Completely insoluble
2. Indiffusable powders—suspending agent required, does not remain suspended long enough for patient
Ex: Aspirin, sulfa drugs, sulfur in topical preps. Salicylic acid, Phenobarbital

16. Formulation of suspension :
Before selecting the additives to be used in the formulation of suspension it is very important to decide whether the particles in suspension are to be flocculated or to remain non flocculated. Following are the additives which are generally used in the formulation of suspension.

17. 1.Flocculating agents
When formulating suspension it must be ensured that the particles are well dispersed in the vehicle. The dispersion can be improved by adding a surfactant which will act by reducing the interfacial tension . For example, if surfactant with negative charge are adsorbed on the particles, prevent or minimizes flocculation in the presence of positive ions because of repulsion of like charges.

18. 2.Suspending agents
suspending are the substances which are added to a suspension to increase the viscosity of the continuous phase so that the particle remain suspended for a sufficiently long time and it becomes easy to measure and accurate dose. while selecting a suspending agent it is not only important that it should increase the viscosity of the system but the popularity,spreadility etc of the final product must also be taken into consideration. Some of the suspending agent used in the formulation include acacia,tragacanth and Na alginate. Na carboxylmethylcellulose in concentration of about 3.5cent is used in injectable suspension.

19. 3.Wetting agent
Wetting agents are the substance which reduce the interfacial tension between the solid particles and liquid medium thus producing a suspension of desired quality. Only minimum amount of wetting agent should be used, excessive amount may lead to foaming or impart and undesirable taste or odour to the suspension.

20. 4. Dispersing agent :
The first step in the formulation of any suspension is to ensure that the particles are dispersed in and wetted by the dispersion medium. In some substance where the surface energy is not sufficient the particles may come together and formed larger particles. To overcome this problem the substance which are used known as dispersing agent.

21. Preservatives :
The presence of suspending agent and the medicaments which are labile for bacterial growth makes it necessary to incorporate a preservative in suspension. Preservative selected should be effective against a wide range of microorganism and should be chemically and physically stable. It should be non toxic and compatible with other added substance. The commonly used preservatives are benzoic acid, sodium benzoate, methyl paraben and propyl paraben.

22. Organoleptic additives
Color, sweetening and flavoring agent are used in the oral suspension. Similarly color and perfumes are incorporated in suspension meant for external application but these must be compatible with other ingredient.

23. Interfacial Properties of Suspended Particles
• To approach a thermodynamically stable system:
ΔF = O by:
reduce interfacial tension–Use
surfactant
reduce interfacial area—Control
flocculation (Using Zeta Potential)
--Flocculated particles: weakly bonded
settle rapidly
no cake
re-suspend
--Deflocculated particles: settle slowly
sediment
difficult to re-suspend

24. Suspending Agents Categorize by: – Rheologic Behavior – Ionic Charge
– Amount used
– Internal or External
– Stable pH range
– Any incompatibilities

25. Examples of Suspending Agents
• Gums and Derivatives
– Acacia
– Tragacanth
– Pectin
– Carbopol
• Clays
– Bentonite
– Veegum

26. Cellulose Derivatives
– Methylcellulose
– Carboxymethyl Cellulose Sodium
– HPMC
– HPC