Biphasic liquid dosage form: SUSPENSION.

 

Biphasic liquid dosage form : SUSPENSION.

What is Suspension?

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-> Suspension are the mixtures containing insoluble solids.
Suspension are heterogeneous, biphasic, thermodynamically unstable liquid items in which a solid particles are uniformly distributed in liquid phase (dispersion medium).
☆Classification of Suspension:-

• Particle size- Colloidal & Coarse.
  • Density of solids - Diffusible & Indiffusible.
  • Arrangement of suspended phase - Focculated & Defocculated
• Route of administration - Internal & External.

1) Colloidal suspensions: When the solid particles are less than 1um in size, suspensions are called colloidal suspensions.
2) Coarse suspensions: When the size of solid particles is from 1um to 50-75 um, these suspensions are termed as coarse suspensions.
3) Suspensions containing diffusible solids: Many of the drug substances are light in weight and possess good wetting properties. After shaking, such drugs remain sufficiently suspended, at least till the time the required dose is removed. These drugs are called diffusible solids.
4) Suspensions containing indiffusible solids: Pharmaceutical substances, such as, aspirin, chalk,calamine, zinc oxide, etc., sediment rapidly after shaking and they do not remain uniformly distributed in the continuous phase. Such substances are called indiffusible solids. Such suspensions are compounded using suspending agents. Increased viscosity of continuous phase reduces the rate of sedimentation and keeps the indiffusible drug suspended for sufficient period of time. Generally, compound powder of tragacanth, (2 g/100 ml) or tragacanth mucilage (1/4 of volume of mixture) is used as suspending agents.

Flocculated suspention

> In flocculated suspension, formed flocs (loose aggregates) will cause increase in sedimentation rate due to increase in size of sedimenting particles. Hence, flocculated suspension sediment more rapidly.

Deflocculated suspensions

>In deflocculated suspension, individual particles are settling.
> Rate of sedimentation is slow, which prevents entrapping of liquid medium which makes it difficult to re-disperse by agitation
This phenomenon called 'caking or 'claying.
> In deflocculated suspension larger particles settle fast and smaller remain in supernatant liquid so supernatant appears cloudy.
5) Route of administration: Suspensions may be for internal use, eg. Mixtures; suspensions not for internal use, eg. inhalations and enemas; or for topical application, eg. lotions and liniment.

Advantages of Suspension:-

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i) Bio-availability of finely dispersed and wet drugs is faster than that of the solid dosage forms. Solid dosage forms require more time for disintegration and de-aggregation.
ii) Large doses of insoluble drugs are easier to swallow in the form of suspensions, than solid dosage forms, eg. antacid and antidiarrhoeal preparations.

iii) The higher surface area of suspended phase is more effective to exert their effect, e.g. insoluble antacids, adsorbents such as kaolin, pectin, etc.

iv) Drugs are chemically more stable in the insoluble state than in the soluble state.
v) Liquid preparations are easy to swallow and are thus more useful for pediatric and
geriatric use.
vi) Solid drugs are less unpleasant to taste than their solutions, eg. Paracetamol, chloramphenicol palmitate.
vii) Suspension is one of the techniques to attain slow and sustained drug release.
viii) It is the choice of dosage form to present an insoluble drug in the liquid form.

Disadvantages of Suspension:-

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i) A number of drugs have some solubility in commonly used solvents and this can lead to physical instability of the suspension.
ii) A drug in reduced state of particle size is thermodynamically less stable and tends
to aggregate. Some drugs undergo physicochemical changes during milling and this makes it difficult to attain desired particle size.
iii) Though a drug in insoluble state is more palatable, due to higher surface free energy fine drug particles could adsorb added flavours and colours and make a system difficult to formulate.
iv) In case of the adsorption of preservatives by solids, liquid system needs additionhigher concentration of preservative.
v) The uniform re-dispersion of sediment determines dose accuracy.

Physical stability of Suspension:-

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Suspensions should contain uniform distribution of fine particles, which should not settle rapidly and if particles do settle the sediment should be readily re-dispersible upon gentle shaking of the container and remain suspended long enough for a dose to be measured. The insoluble suspended particles, whether diffusible or indiffusible, settle at the bottom of the container. The rate of settling or sedimentation of particles can be described by Stoke s law:

V =  d²(Ps- Pp)g ÷ 18n

Where, V is the terminal velocity of a spherical particle,
d is the diameter of particle
Ps( Ro s) and Pp (Ro p)are the densities of dispersed phase and dispersed medium respectively, n is the viscosity of dispersed medium.
g is the acceleration due to gravity, and
n is the viscosity of dispersed medium.

The rate of settling is directly proportional to the diameter of suspended particles. However, reduction in size is not always possible. Particles with size 2-5 um show Brownian motion.
The suspended phase and medium should be of equal density. Vehicles such as syrup, IP, and sorbitol solution, are used to adjust the density. Increasing the viscosity of external phase is the usual approach to reduce the rate of sedimentation in pharmaceutical suspensions. Various types of suspending agents including gum acacia, tragacanth, methylcellulose, bentonite, carbomer, etc. are usually used for this purpose. Suspensions containing diffusible drugs are formulated without the use of suspending agents. The indiffusible suspension requires suspending agent.

Monophasic liquids