Suspension

PHRM 210

Disperse systems

• The term ‘disperse system’ refers to a system in which one substance (the dispersed phase) is distributed in discrete units throughout a second substance (the continuous phase or vehicle).

• Each phase can exist in solid, liquid, or gaseous state.

Classification of disperse systems based on particle size:

Class Particle Size Examples

Molecular <1 nm Ionsdispersion Glucose

Colloidal 1nm to Milkdispersion 1µm

Coarse >1 µm Emulsionsdispersion Suspensions

Suspensions

• A suspension is a coarse dispersion in which a solid is dispersed in a continuous liquid phase.

• It is a coarse dispersion in which insoluble solid particles in a fine state of subdivision are dispersed in a liquid medium.

Suspensions

• The dispersed solid phase is sometimes referred to as the internal (disperse) phase and the continuous phase as the external phase. Suspensions may be either aqueous or non-aqueous.

• Pharmaceutical colloidal suspension is also possible, for example aluminum hydroxide and magnesium hydroxide suspensions.

Examples

• Antacid oral suspensions• Antibacterial oral suspension• Dry powders for oral suspension (antibiotic)

Physical properties of suspension

• The product must remain sufficiently homogenous for at least the period between shaking the container and removing the required amount.

• The sediment produced on storage, if any, must be easily resuspended by moderate agitation of the container.

Physical properties of suspension

• The product may be required to be thickened in order to reduce the rate of settling of the particles. The resulting viscosity must not be so high that removal of the product from the container and transfer to the site of application are difficult.

• Suspended particles should be small and uniformly sized in order to give a smooth, elegant product, free from a gritty texture.

Basic characters of suspension• Particles should settle slowly.• Formulation should allow the easy

redispersion of sedimented particles.• A flocculated suspension is desirable than a

deflocculated suspension.• A suspension should not be too viscous to

reduce the sedimentation rate.• Suspension for internal use must be palatable,

for external use must be free from gritty particles.

Reasons for oral suspensions• Certain drugs are chemically unstable when in

solution but stable when suspended.• In many patients, the liquid form is preferred

over the solid form of same drug due to ease of swallowing liquids.

• Resistance to hydrolysis and oxidation is generally good in suspensions when compared with that in respective aqueous solutions.

• The masking of disagreeable taste of poorly tasting drug e.g. chloramphenicol.

Disadvantages

• Sedimentation and compaction of sediment (of dispersed phase) in suspension is known as caking, frequently causes problems that are not always easy to solve.

• Product is liquid and relatively bulky compared to solid dosage forms.

• They are difficult to carry and there are chances of breakage of container with the complete loss of contents.

Classification: Flocculated

• Particles form loose aggregates and form a network like structure.

• The rate of sedimentation is high.• Sediment is formed rapidly & redisperse

easily.

Classification: Flocculated

• Sediment is loosely packed and a hard cake does not form.

• Supernatant liquid is clear.• The floccules stick to the sides of the bottle.• Suspension is not pleasing in appearance.

Classification: Deflocculated

• Particles exist as separate entities.• The rate of sedimentation is slow.• Sediment is slowly formed and difficult to

redisperse.• Sediment is very closely packed and a hard

cake is formed.

Classification: Deflocculated

• Supernatant liquid is not clear.• The floccules do not stick to the sides of the

bottle.• Suspension is pleasing in appearance.

Fig: The sediment behavior of flocculated and deflocculated suspensions

Flocculated

Deflocculated

Classification: Pharmaceutical Uses Oral suspensions• These suspensions are to be consumed by the

patient by oral route. Oral suspensions generally contains flavoring agent & sweetening agent to mask the bitter taste of the drug.

• Nowadays, suspensions are available in the market in dry powder form and these are reconstituted by adding water . For example, antibiotics as suspension for pediatric use.

Classification: Pharmaceutical Uses Parenteral suspensions• The suspensions which are administered by

parenteral route are called parenteral suspensions.

Ophthalmic suspensions• These are not commonly used as compared to

eye-drops. These are prepared only in those cases, when the drug is insoluble in the desired solvent or unstable in liquid forms.

Classification: Pharmaceutical Uses

Suspensions for external use• These suspensions are intended for external

use. For example lotions, inhalations, ear drops etc. These suspensions contain very small particles to avoid grittiness.

Packaging & storage

• Should be packaged in wide mouth containers having adequate air space above the liquid.

• Should be stored in tight containers protected from: freezing and excessive heat & light.

• Label "Shake Before Use" to ensure uniform distribution of solid particles and thereby uniform and proper dosage.

Formulation of suspension

• Following excipients are commonly used in the preparation of suspensions:

- Suspending agents- Flocculating agents- Wetting agents

Suspending agents

• These are the substances which are added to a suspension to increase the viscosity of the continuous phase so that particles remain suspended for a sufficiently long time and it becomes easy to measure the accurate dose.

• Example:Acacia, Tragacanth (Natural)CMC, Na-CMC (Artificial)

Flocculating agents

• These substances prevent the formation of compact sediment- that is difficult to redisperse. For example

ElectrolyteSurfactantsPolymers

Wetting agents

• Make the powder more penetrable through the continuous phase by displacing the air around the particles.

• Example :Glycerin, alcohol, glycol etc.

Evaluation of suspensions

• Two parameters are commonly used:- Sedimentation volume- Degree of flocculation

Sedimentation volume

• This parameter, described by the symbol F, is defined as the ultimate volume of the sediment, Vu, divided by the original volume, Vo, of the suspension before settling.

Vu

Vo

F =

Sedimentation volume• The sedimentation volume, F, of a product

may have a volume of less than 1, more than 1, or equal to 1.

• When F=1, the sediment is equal to the total volume of the suspension and the product is said to be in a state of ‘flocculation equilibrium’. Such a product is quite acceptable from a pharmaceutical standpoint because, on standing, it shows no sediment or clear supernatant.

Degree of flocculation

• A better parameter for evaluating flocculation in a suspension is the degree of flocculation, β, which describes the relationship between the sedimentation volume of the flocculated suspension, F, to the sedimentation volume of the same suspension when deflocculated, Fα.

Vu

Vo

F = V Vo

F =

Degree of flocculation

• The ratio of F to Fα is the degree of flocculation, β :

• Substituting for F and Fα we obtain-

F

F

=

Vu

V

=

=Ultimate sediment volume of flocculated suspension

Ultimate sediment volume of deflocculated suspension

Stoke’s law

• Most important law that controls the formulation of suspensions.

V =2r2 (P-P0) g

9n

Stoke’s law

In equation:V = terminal velocity of fall of an average particle in the dispersion. r = radius of the particles P = density of dispersed phasePo= density of the continuous phase

g = gravity constant η = viscosity of the dispersion medium

Stoke’s law

• Particles are rigid and spherical and of uniform sized

• Suspensions are dilute (<2% w/v)• Particles do not flocculate i.e. free settling

occurs.• No brownian movement• No electrical effects

Stoke’s law

In case of pharmaceutical preparations-• Dispersion phase in suspension spherical and

in emulsion particles are not rigid as they are liquid

• Their sizes are not uniform

So Stoke’s law is not exactly for pharmaceutical dispersions.

Stoke’s law

• But this law can be used to give good indication of

-- factors that contribute to settling of particles-- where adjustment is possible for better

preparation