Suspension

Table of contents

• Suspension
• Classification of suspension
• Formulation of Suspension
• Methods of preparation of dispensing suspensions

 Suspension 

• Suspension are biphasic liquid dosage form in which finely divided solid particles (ranging from 0.5µm to 5µm) are suspended or dispersed in liquid medium.
• Solid particle act as disperse phase.Liquid vehicle act as continuous phase.
• Suspensions are meant for oral use, parentral use, external use.
• Suspensions facilitate administration of insoluble, unpleasant substances in a form which is pleasant in taste.
• It is thermodynamically stable.
• It is also suitable for dermatological material to the skin andmake us membrane and for parental administration of insoluble drugs.

Qualities of Good Suspension:

A well formulated suspension should have the following properties :

• The dispersed particles should not settle readily and the settled particles should redisperse immediately on shaking.
• The particles should not form a cake on settling.
• The viscosity should be such that the preparation can be easily poured.
• It should be chemically stable.
• Suspensions for internal use must be palatable and suspensions for external use must be free from gritty particles and possess other characteristics required for external preparations.

Advantages of Suspensions:

• Suspension improve chemical stability of certain drugs ( e.g. Procaine penicillin G).
• Drug in suspension have higher rate of bioavailability. (Solution> Suspension > Capsules > Compressed tablet > Coated tablet).
• Duration and onset of action can be controlled. (e.g.Protamine Zinc Insulin Suspension.)
• Suspension can mask upleasant taste of drug. (e.g. Chloramphenicol).
• Suspension is usually used for drug which is insoluble or poorly soluble.(e.g. prednisolone).
• Drug which degrade in aqueous solution maybe suspended in a non aqueous phase. (e.g. Tetracyclin hydrochloride is suspended in a fractinated coconut oil for use).
• Suspensions is a ideal dosage form for patient who cannot swallow tablet or capsule.
• Suspension means for external application should have very small particle size to avoid gritty feeling to the skin.

Disadvantages of Suspension:

• Physical stability sedimentation and compaction can cause problem.
• It is bulky therefor sufficient care must be taken duringh andling and transport.
• It is difficult to formulate.
• Uniform and accurate dose cannot be achieved unlesss uspension are packed in unit dosage form.

Classification of suspension

1)Based on Pharmaceutical use:

     a)oral suspension.
     b)parental suspension.
     c)external suspension

     d)phthalmics suspension.

a)Oral suspension.

• Antibiotic preparation, antacid and radiopaque suspension contain relatively high amount of suspended material for oral administration.
• The vehicle maybe syrup, sorbital ro a gum-thickened, water containing artificial sweatener because in addition to ingredient safety, test and mouthfeel are important. (e.g. chloramphenicol suspension)
• Limited shelf ife (low chemical stability of the insoluble drug) the dosage form may be prepared as a dry granulation or powder mixture that is reconstituted with water piror to use.(e.g. antibiotic suspension).

b)parental suspension.

• The solid content of parental suspension is usually between 0.5 and 5.0 % w/v except for insoluble form of penicillin in which concentration of the antibiotic may exceed 30% w/v.
• The sterile preparation are designed for intramuscular,intradermal,intra-lessional,intra-articula, or subcutaneous administration
• Common vehicle used for parental suspension include preserved 0.9%w/v saline solution or a parentally acceptable vegetable oil.

c)external suspension.

• The externally applied "shake lotion" is the oldest example of a pharmaceutical suspension.
• Calamine lotion USP as well as other dermatological preparation.
• Many useful suspending agents where first introduced in topical formulation.
• Various Pharmaceutical vehicles have been used in the preparation of topical lotion including diluted oil in water or water in oil emulsion bases, dermatological paste, magmas and clay suspension.

 d)Ophthalmic suspension.

• Ophthalmic suspension prepared in sterile manner.Vehicle employed in essential isotonic and aqueous in composition.
• Mucilages, Magmas, gel and sometime aerosol also included would be dry powder to which a vehicles is added at the time of dispensing.
• For most part only aquases suspension are discussed and little attention is paid to oil or aerosol prepellants as vehicle suspension, this discussion is limited to suspension with particle having diameter greater than 0.2µm.

2)based on proportion of solid particle.

1. Dilute suspension (2 to 10% w/v solid)e.g. cartisone acetate.
2. Concentrated suspension (50% w/v solid)e.g. zinc oxide suspension.

3)based on electrokinetic nature of solid particle.

1. Flocculated suspension.
2. Deflocculated suspension.

4) based on size of the salt particle.

1. Collaidal suspension ( <1 micron).
2. coarse suspension (>1micron).
3. Nano suspension(10 nm).

Formulation of suspension

1. Floculating agents. 
2. suspending/thickening agents. 
3. wedding agents.
4. dispersing agents.
5. preservative.
6. organoleptic additives.

1)Floculating agents.

• In suspensions, the solid particles are well dispersed in dispersion medium i.e., vehicle. The dispersion can be improved by adding a surfactant or protective colloid which acts as flocculating agent.
• The flocculating agent acts by reducing the surface tension and thereby improving the dispersion of solids and minimise flocculation. 
• e.g., sodium lauryl sulphate, tweens, spans and carbowaxes, etc. are commonly used as flocculating agents.

2) suspending agents/Thickening agents:

• These are hydrophilic colloids which form colloidal dispersions with water and increases the viscosity of the continuous phase, so that the solid particles remain suspended in it for a sufficient long time to measure a uniform accurate dose.
• The thickening agents used to stabilise suspensions are classified into three major groups-polysaccharides, inorganic agents and synthetic compounds.

    1.Polysaccharides: 

         Two types of polysaccharides are used nowa days. These are:

           a) Natural polysaccharides:

                 Gam acacia

                 Tragacanth 

                 Starch 

                 Sodium alginate

           b) semisynthetic:

                Methyl cellulose.

                Sodium carboxymethyl 

cellulose.

                Microcrystalline cellulose.

     2. Inorganic agents 

               Clay.

               Aluminium hydroxide.

     3. Synthetic compound.

 (a)Carbomer (carboxy vinyl polymer):

   It is used as a thickening agent in the concentration of 0.1 to 0.4 per cent for internal and external preparations.

     (b) Colloidal silicon dioxide: 

   It is a white non-gritty powder and acts as a suspending agent in the concentration of 1.5 to 4%.

3) wetting agents.

• These are the substances which reduce the interfacial tension between the solid particles and liquid medium, thus producing a suspension of required quality. 
• This may be achieved by adding a suitable wetting agent which is adsorbed at the solid/liquid interface in such a way that the affinity of the particles for the surrounding medium is increased and the interparticular forces are decreased. 
• For example, alcohol in tragacanth mucilage, glycerin in sodium alginate or bentonite dispersion and polysorbate in oral and parenteral suspensions.
• The excessive use of wetting agent may cause foaming or may give bad taste or odour to the suspension.

4)Preservatives: 

• A suitable preservative is needed to preserve suspensions against bacterial growth.
• Preservatives selected should be effective against a wide range of microorganism. 
• Benzoic acid, sodium benzoate, methyl paraben and propyl paraben are commonly used as a preservative in suspensions.

5)Organoleptic additives:

• Colouring agents, sweetening agents and flavouring agents are generally incorporated in oral suspensions.
• A suitable perfume and colour is incorporated in suspensions which are meant for external use.

Methods of preparation of dispensing suspensions

      The suspensions are divided into 4 types according to its method ofdispensing:

1. Suspensions containing diffusible solids.
2. Suspensions containing indiffusible solids.
3. Suspensions containing precipitate-forming liquids.
4. Suspensions produced by chemical reactions.

1.Suspensions Containing Diffusible Solids

• There are certain insoluble powdered substances which are light in weight and readily mix with water and remain suspended throughout the liquid for sufficient long time after shaking. Such substances are known as diffusible solids. 
• For example, calcium carbonate, light magnesium carbonate, magnesium trisilicate, rhubarb powder and light kaolin.

General   method  of   dispensing

1. Carefully tare the container. 
2. Finely powder the solid ingredients.
3. Mix the insoluble powders in a mortar and add enough vehicle to make a smooth cream.
4. Add more of vehicle to make it pourable.
5. Examine the suspension carefully and if it contains foreign particles, strain through a muslin cloth into a tared container.
6. Rinse the mortar and pestle with successive volume of vehicle until they are quite clean. Transfer the rinsings to the bottle.
7. Add any liquid ingredient.
8. Add more of vehicle to produce the required volume and mix thoroughly by shaking the bottle.

2.Suspensions Containing Indiffusible  Solids

 Indiffusible solids are those substances which do not dissolve in water and do not remain evenly distributed in the vehicle for sufficient long time to ensure uniformity of dose. The examples of some of the indiffusible solids are given in table.

General method of dispensing (using compound tragacanth powder.

1. Finely powder all the ingredients. 
2. Mix them together in a mortar and add compound tragacanth powder.
3. Measure 3/4th of the vehicle and triturate to form a smooth cream. 
4. Examine the suspension carefully and, if it contains any foreignparticles, strain through a muslin piece into a tared bottle. 
5. Rinse the mortar with small quantity of vehicle to clean it. Transfer the rinsings to the bottle.
6. Add any liquid ingredient.
7. Add more of the vehicle to produce the required volume.

3.Suspensions Containing Precipitate-forming Liquids:

  There are certain liquid preparations that is precipitated on additionto water. For example, compound benzoin tincture, benzoic tincture, myrrh tincture and tolu tincture. These liquids are not only insoluble in water but they form indiffusible precipitates particularly when salts are present. They contain resinous matter and when it is mixed with water, it leads to precipitation of resin and may stick to the sides of the bottle which will be difficult to rediffuse by shaking. To prevent this, a protective colloid is dispersed in the vehicle before tincture is added. Tragacanth mucilage (1/4th of the total volume) or compound tragacanth powder (2 g/100 ml) is commonly used as protective colloid.

General method of dispensing (using compound tragacanth powder):

1. Finely powder the indiffusible solid and diffusible solid in the mortar. Mix them with compound tragacanth powder in a mortar.
2. Measure half of the vehicle and incorporate a small amount of it to the powders with trituration until a smooth cream is formed.Then add the remaining part of the vehicle.
3. Measure the precipitate forming liquid in a dry measure and add it in a slow stream in the centre of the cream with rapid stirring. 
4. Dissolve the soluble ingredient (if present) in sufficient amount of vehicle out of the remaining half of the vehicle. Add it slowly with constant stirring to the cream to avoid local high concentrations that may neutralise the effect of suspending agent.
5. Examine the contents of the mortar critically for foreign parti cles. If these are present, strain the suspension through muslin piece into a bottle.
6. Add more of vehicle to rinse the mortar and transferring the rinsing to the bottle. 
7. Add any liquid ingredient.
8. Add more of the vehicle to produce the required volume.

General method of dispensing (using tragacanth mucilage):

    Tragacanth mucilage is used when the vehicle is water or chloroform water.

1. Mix the tragacanth mucilage with an equal volume of the vehicle. 
2. Measure the precipitate-forming liquid in a dry measure and pour slowly into the centre of the mucilage with constant stir ring.
3. Dissolve the solid substance if any, in about 1/4th of the vehicle and mix it with above mixture.
4. Step 5, 6, 7 and 8 are same as that of general method of dispensing for preparing suspension containing precipitate forming liquids using compound tragacanth powder.

(4)Suspensions Produced by Chemical Reactions

  In this type of preparation of suspensions, the highly diluted solu tions of reactants are mixed together so as to form very finely divided precipitates that can be easily distributed throughout the liquid by shak ing. The precipitates so formed are diffusible in nature. Hence, there is no need of adding any suspending agent.

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