SUSPENSIONS

 Definitions:

British Pharmacopoeia defined oral suspensions as oral liquids containing one or

more active ingredients suspended in a suitable vehicle.
Suspended solids may slowly separate on standing but are easily redispersed.
The rate of settling and the ability to get redispersed is dependent on whether the
preparation is a diffusible or indiffusible suspension.

 Diffusible suspensions
These are suspensions containing light powders which are insoluble, or only very
slightly soluble in the vehicle, but which on shaking disperse evenly throughout
the vehicle for long enough to allow an accurate dose to be poured.

 Indiffusible suspensions
These are suspensions containing heavy powders which are insoluble in the
vehicle and which on shaking do not disperse evenly throughout the vehicle long
enough to allow an accurate dose to be poured.
Advantages of Suspensions as Dosage Forms

 Insoluble derivatives of certain drugs may be more palatable than their

soluble equivalent as seen with suspensions of the insoluble chloramphenicol
palmitate.
 Insoluble derivatives of drugs may be more stable in the aqueous vehicle than
the equivalent soluble salt.
 Suspended insoluble powders are easy to swallow.
 Bulky insoluble powders such as Kaolin BP and Chalk BP can be administered
in suspension and can act as adsorbents of toxins in the gastrointestinal tract.
 Suspended drugs will be more rapidly absorbed from the gastrointestinal tract
than the equivalent solid dosage form (although absorption will be slower
than from the equivalent solution).
 Lotions that are suspensions leave a thin layer of medicament on the skin. The
liquid part of the suspension evaporates, giving a cooling effect to the skin and
leaving the thin layer of powder behind (for example Calamine Lotion BP).
 Sustained release preparations can be prepared in suspension (but because of
the difficulty of formulation they are rarely encountered).
Disadvantages of Suspensions as Dosage Forms

 They must be well shaken prior to measuring a dose.

 The accuracy of the dose is likely to be less than with the equivalent solution.

 Conditions of storage may adversely affect the disperse system and in the
case of indiffusible solids clumping may occur, leading to potential dosing
inaccuracy.

 Like all liquid dosage forms, they are always much larger and more bulky than
their comparable solid formulations. This makes them heavy and difficult to
transport. Coupled with this is the fact that, traditionally, pharmaceutical
liquids are packed in glass bottles. These are obviously prone to breakage
which can be hazardous and cause the loss of the preparation.
Desirable properties of pharmaceutical suspensions

 A suspension should be viscous enough to ensure slow particle settling but

should not be too viscous to make pouring or passage through syringe needle
difficult

 The medicament, after shaking, should remain uniformly suspended long

enough to ensure accurate withdrawal of dose

 The sedimented particles should be easily re-dispersed on shaking the

container and must not form a hard cake

 The suspended particles should be small and have narrow size range in order
to give a smooth elegant product, free form gritty texture or irritation if
injected or instilled into the eyes

 It must not have objectionable colour or odour

Formulation of Suspensions

Mixtures containing diffusible solids

Diffusible solids are powders that are light and easily wettable and are easily
dispersed when shaken in the chosen vehicle. They remain distributed for long
enough for a dose to be measured.

Such powders include but not limited to Light kaolin, Magnesium trisilicate,
Magnesium carbonate light or heavy, Phenolphthalein etc.
Extemporaneous Preparation of Suspension Containing a Diffusible Solid

 Check the solubility in the vehicle of all solids in the mixture.

 Calculate the quantities of vehicle required to dissolve any soluble solids.

 Weigh all solids on a Class II or electronic balance.

 Dissolve all soluble solids in the vehicle in a small glass beaker

 Mix any insoluble diffusible powders in a porcelain mortar using the ‘doubling-
up’ technique to ensure complete mixing

 Add a small quantity of the vehicle (which may or may not be a solution of the
soluble ingredients) to the solids in the mortar and mix using a pestle to form a
smooth paste.

 Add further vehicle in small quantities, and continue mixing until the mixture in
the mortar is of a pourable consistency.
 Transfer the contents in to a pre calibrated bottle

 Rinse out the mortar with more vehicle and add any rinsings to the bottle

 Add remaining liquid ingredients to the mixture in the bottle. (These are
added now, as some may be volatile and therefore exposure whilst mixing
needs to be reduced to prevent loss of the ingredient by evaporation.)

 Make up to final volume with vehicle, and label ready to be dispensed to

the patient.
MIXTURES CONTAINING INDIFFUSIBLE SOLIDS

Some powders are not easily wetted and when dispersed in water do not remain
evenly distributed in the vehicle long enough to ensure uniformity of dose. A
third component, otherwise called a suspending agent is thus added to facilitate
its dispersion.

The “wettability” of powdered drug material in a coarse dispersion is a function

of the hydrophobicity of the dispersed phase. While some insoluble solids may
be easily wetted by water e.g. talc, some particles form large porous clumps
within the liquid while others remain on the surface and become attached to the
upper part of the container.

The displacement of adsorbed air from the surface by surface by wetting agent
will decrease the interfacial tension between the solid and the liquid and thus
promote wetting of the former by the latter
Wetting agents commonly used in dispersed systems

 Surface active agents

The dual hydrophilic/hydrophobic structure of these agents provide them the
ability to cause falls in interfacial tension between the solid and liquid phases in
disperse systems providing wetting. Examples include the polysorbates (tweens)
and sorbitan esters (spans) used for internal preparations while sodium lauryl
sulphate and quilliar extracts are used externally.

 Hydrophilic colloids
Hydrophilic colloids like acacia, bentonite, tragacanth, alginates and cellulose
derivatives act by imparting a hydrophilic character to the solid where they
behave as protective colloids by coating the solid hydrophobic particles with a
multimolecular layer and thus promote wetting.

 Solvents
Water miscible materials such as alcohol, glycerol, reduce the liquid/air interfacial
tension. They penetrate the loose agglomerates of powder displacing the air from
the pores of the individual particles, thus enabling wetting.
Extemporaneous Preparation of Suspension Containing a
Diffusible Solid

Preparation of suspensions containing indiffusible powders is

similar to the of diffusible powders except that a predetermined
quantity of a suspending agent need to be triturated with the
powder prior to addition of the vehicle.

Suspending agent
This is an inert material that retards the sedimentation of the
undissolved and indiffusible drug material by increasing the
viscosity, density and a yield value of the vehicle used in
formulating the suspension.
Classes of suspending agents

 Polysaccharides
• Natural polysaccharides e.g. acacia, tragacanth, starch
powders
• Semi-synthetic polysaccharides, chemically modified
celluloses e.g. methylcellulose, hydroxyprophyl
methylcellulose

 Inorganic agents
• Natural clays e.g. bentonite BPC, aluminium magnesium
silicate
• Hydrated aluminium hydroxide

 Synnthetic compounds
Example carboxypolymethylene (carbopol(R))
Powders that require use of a suspending agent

•Acetylsalicylic acid
•Barbitone
•Benzoic acid
•Bismuth salicylate
•Chlorbutol
•Phenacetin
•Phenobarbitone
•Prepared chalk
•Quinine sulphate
•Quinine salicylate
•Salicylic acid
•Sulphadimidine
•succinylsulphathiazole
Use of tragacanth as suspending agent

Three concentrations commonly used are:

1. 0.2% of tragacanth powder
2. 2 % of compound tragacanth powder
3. ¼ of the volume of mixture when tragacanth mucilage is used

Compounding: The indiffusible solid is triturated with an appropriate

quantity of the suspending agent and the vehicle is thereafter added to
effect its dispersion

Container type: Narrow mouthed, screw capped, colorless, Plain bottle

Print color of main label (outline) : Black

Auxiliary label: Shake the Bottle

Examples:

Use tragacanth, compound tragacanth or tragacanth mucilage to prepare the following

Rx
Prepared chalk 0.5 g
Tincture catechu 0.5 ml
Cinnamon water ad 10 ml
Fiat mistura
Mitte 100 ml
Sig. Secundis Horis Summenda
 Suspension Types

A stable suspension can be redispersed homogenously with moderate shaking

and can be poured easily through out its shelf life, with neither the particle-size
distribution, the crystal form, nor the physiological availability of the suspended
active ingredient changing appreciably with time.

Flocculated suspension:

The suspended particles are bonded together physically to form a

loose, semi rigid structure and are easy to redisperse upon settling

Nonfloccucated suspension:

The suspended particles remain as individuals unaffected by

neighboring particles and are affected only by the suspension vehicle and
are difficult to redisperse after settling.
Exercises

Send 50 ml of potassium permanganate of which when one part is diluted with

seven parts of water the solution becomes 1 in 8000 concentration

Send 50 ml of potassium permanganate of which when one part is diluted to

seven parts with water the solution becomes 1 in 8000 concentration

Send 80ml of 0.2% potassium permanganate solution and give directions to use
1 in 20 dilution as a wound dressing et mane

Solution
0.2% = 0.2 g in 100ml solution
X g in 80ml
X = (0.2 x 80)/100 = 0.16 g
0.16 g of potassium permanganate to be dissolved in 80 of purified water

1 in 20 dilution = 1ml in 20ml or 5ml in 100ml

Direction: Two 5ml spoonful to be diluted to make a half tumblerful of solution

with water and used as wound dressing every morning (Note a tumblerful is
200ml)
Send 50ml of 4% copper sulphate solution and label with direction for preparing
1 litre quantities of 1 in 2500 solution

Hyoscine hydrobromide 0.001g

Chloroform water ad 10 ml
Make a mixture
Sig: One teaspoonful p.r.n.

Hyoscine hydrobromide 0.001g

Chloroform water ad 10 ml
Make a mixture
Send 80 mls
Sig: One teaspoonful t.d.s

Hyoscine hydrobromide 0.0001g

Chloroform water ad 10 ml
Make a mixture
Send 80 mls
Sig: One teaspoonful t.d.s
Rx
Turpentine oil 15ml
Acacia in a fine powder 7.5g
Distilled water ad 100ml
Send 50ml
Sig: Mor dict.

Send 60ml of Liquid Paraffin 15%v/v emulsion preserved with chloroform water

You are asked to prepare 100ml of emulsion containing Liquid Paraffin BP 36%,
Amaranth BP 0.5% and Syrup BP 10%. How much Acacia BP would be needed to
prepare the primary emulsion?

Rx
Liquid Paraffin 10 ml
Vanillin 1g
Purified water to 60 ml
Preserve the product using chloroform water
Label: The Enema
Give an appropriate direction for use
Magnesium Sulphate 2.5%
Magnesium Carbonate 1.5%
Peppermint water to 100%
Send 50ml

Send 80ml Magnesium Trisilicate Mixture BP

Sig: 10ml t.d.s. ex aqua

Rx
Sodium bicarbonate 20.00 g
Tartaric acid 10.08 g
Citric acid 8.92 g
Sugar 6.00 g
Send 15g
Label: The Effervescent powder
Sig: take 5 g in water p.c
Rx
Sodium Chloride 3.5 g
Potassium chloride 1.6 g
Sodium citrate 2.9 g
Anhydrous glucose 20.0 g
Label: Oral rehydration salt
Mitte 10 g
Label with instruction for the patient to take an equivalent of 625 mg of Sodium
chloride in water p.r.n.

Rx
Zinc Oxide 1 part
Starch in powder 1 part
Purified talc 2 parts
Mitte 15 g
Sig: apply to the affected parts.

Send 5 powders each containing

Aspirin 0.25
Phenacetin 0.25
Sig: i b.d