Pharmaceutical Technology

1. Suspensions
11/9/2022 BA-FP-JU-C

2. suspensions
• A suspension: is a disperse system in which one
substance (the disperse phase) is distributed in
particulate form throughout another (the
continuous phase) (i.e. at least 2 phases).
• According to the particle size of the dispersed
phase, suspensions are divided into:
 Coarse suspension: which is a dispersion of particles
with a mean diameter greater than 1 µm.
 Colloidal suspension is a dispersion of particles with a
mean diameter less than 1 µm.
11/9/2022 BA-FP-JU-C

3. Pharmaceutical application of suspensions
Why suspensions?
Against solid dosage forms:
• If patient has a difficulty of swallowing solid dosage forms (a
need for oral liquid dosage form).
• Faster rate of dissolution and oral absorption than solid dosage
forms, yet slower than solutions.
• Bulky insoluble powders as kaolin or chalk are better
formulated as suspensions so that they are easier to take.
11/9/2022 BA-FP-JU-C

4. Pharmaceutical application of suspensions
Why suspensions?
Against solutions:
• Drugs that have very low solubility are usefully formulated as
suspensions.
• Drugs that have an unpleasant taste in their soluble forms (e.g.,
chloramphenicol (soluble) vs. chloramphenicol palmitate (insoluble )).
• Prolongation of effect (e.g. I.M and S.C. suspensions).
• Stability and instability issues:
 Insoluble forms of drugs may prolong the action of a drug by
preventing rapid degradation of the drug in the presence of water (e.g.,
Oxytetracycline hydrochloride (soluble, hydrolyses rapidly) vs
oxytetracycline calcium salt (insoluble, stable).
 Non-aqueous suspensions (tetracycline hydrochloride in coconut oil)
 Reconstitution (ampicillin suspension).
11/9/2022 BA-FP-JU-C

5. Properties of a good pharmaceutical suspension
• There is ready redispersion of any sediment which
accumulates on storage.
• After gentle shaking, the medicament stays in
suspension long enough for a dose to be accurately
measured.
• The suspension is pourable.
• Particles in suspension are small and relatively uniform
in size. so that the product is free from a gritty texture.
11/9/2022 BA-FP-JU-C

6. Formulation of suspensions
Formulation problems
1. Sedimentation.
2. Thermodynamic instability.
3. Wetting.
11/9/2022 BA-FP-JU-C

7. Sedimentation
• The factors affecting the rate of sedimentation are in Stokes'
equation:
• Where v= velocity of sedimentation of a spherical particle of radius r,
and density σ, in a liquid of density ρ, and viscosity ŋ, and where g is
the acceleration due to gravity.
11/9/2022 BA-FP-JU-C

8. Thermodynamic instability
• Interfacial free energy (IFE).
• IFE = Interfacial tension * surface area
• Flocculation
• Aggregation
11/9/2022 BA-FP-JU-C

9. Flocculation
The natural tendency of particles towards aggregation will determine the
properties of a suspension. Whether or not a suspension is flocculated
or deflocculated depends on the relative magnitude of
repulsive/attractive forces between particles.
• Deflocculated suspension: the dispersed solid particles remain
separate and settle slowly. However, the sediment that eventually
forms is hard to redisperse and is described as a 'cake' or clay.
• Flocculated suspension, individual particles aggregate into clumps or
floccules in suspension. Because these flocs are larger than individual
particles, sedimentation is more rapid, but the sediment is loose and
easily redispersible. Excess flocculation may prevent 'pourability' due
to its effect on rheological properties.
The ideal is to use either a deflocculated system with a sufficiently high
viscosity to prevent sedimentation, or controlled flocculation with a
suitable combination of rate of sedimentation, type of sediment and
pourability.
11/9/2022
BA-FP-JU-C

10. The insoluble medicament may be :
• Diffusible solids (dispersible solids): These are insoluble solids that
are light and easily wetted by water. They mix readily with water,
and stay dispersed long enough for an adequate dose to be
measured. After settling they redisperse easily. Examples include
magnesium trisilicate, light magnesium carbonate, bismuth
carbonate and light kaolin.
• Indiffusible solids: Most insoluble solids are not easily wetted, and
some particles may form large porous clumps in the liquid,
whereas others may remain on the surface. These solids will not
remain evenly distributed in the vehicle long enough for an
adequate dose to be measured. They may not redisperse easily.
Examples for internal use includes aspirin, phenobarbital,
sulfadirnidine and chalk, and for external use calamine,
hydrocortisone, su1phur and zinc oxide.
11/9/2022 BA-FP-JU-C
Wetting

11. Wetting
• Because of the high interfacial tension between indiffusible
solids and water; air may be trapped in these poorly wetted
particles which causes them to float to the surface of the
preparation and prevents them from being readily dispersed
throughout the vehicle.
• Wetting of the particles can be encouraged by reducing the
interfacial tension between the solid and the vehicle, so that
adsorbed air is displaced from solid surfaces by liquid.
• Suitable wetting agents have this effect, but decrease inter-
particular forces thereby affecting flocculation.
11/9/2022 BA-FP-JU-C

12. Wetting
Wetting agents:
 Hydrophilic colloids such as acacia and tragacanth can act as
wetting agents. However, care should be taken when using these
agents as they can promote deflocculation.
 Intermediate HLB (hydrophilic-lipophilic balance) surfactants
such as polysorbates (tweens) and sorbitan esters (spans) are
used for internal preparations. Sodium lauryl sulphate and
quillaia tincture are used in external preparations.
 Solvents such as ethanol, glycerol and the glycols also facilitate
wetting.
11/9/2022 BA-FP-JU-C

13. Suspending agents
• Suspending agents increase the viscosity of the vehicle, thereby
slowing down sedimentation.
• Most agents can form thixotropic gels which are semisolid on
standing, but flow readily after shaking.
• Care must be taken when selecting a suspending agent for oral
preparations.
• Suspending agents can be divided into five broad categories:
natural polysaccharides, semi-synthetic polysaccharides, clays,
synthetic thickeners and miscellaneous compounds.
11/9/2022 BA-FP-JU-C

14. Suspending agents
Natural polysaccharides
• The main problem with these agents is their natural variability
between batches and microbial contamination.
• These materials should not be used externally as they leave a sticky
feel on the skin.
• They include tragacanth, acacia gum, starch, agar, guar gum,
carrageenan and sodium alginate.
• Tragacanth:
 Is a widely used suspending agent and is less viscous at pH 4-7.5.
 As a rule: 0.2g tragacanth powder is added per 100 mL suspension or
2g compound tragacanth powder per 100 mL suspension. Compound
Tragacanth Powder BP 1980 contains tragacanth, acacia, starch and
sucrose and so is easier to use.
 Tragacanth powder requires to be dispersed with the insoluble
powders before water is added to prevent clumping .
11/9/2022 BA-FP-JU-C

15. Suspending agents
Semi-synthetic polysaccharides
• These are derived from the naturally occurring polysaccharide
cellulose.
• Examples include
 Methylcellulose (Cologel ®, Celacol®)
 Hydroxyethylcellulose (Natrosol 250®)
 Sodium carboxymethylcellulose (Carmellose sodium®)
 Microcrystalline cellulose (Avicel®).
11/9/2022 BA-FP-JU-C

16. Suspending agents
Clays
• These are naturally occurring inorganic
materials which are mainly hydrated silicates.
• Examples include bentonite and magnesium
aluminium silicate (Veegum®).
11/9/2022 BA-FP-JU-C

17. Suspending agents
Synthetic thickeners:
• These were introduced to overcome the variable quality of
natural products.
• Examples include:
 Carbomer (Carboxyvinyl polymer, Carbopol®),
 Colloidal silicon dioxide (Aerosil®, Cab-o-sil®)
 Polyvinyl alcohol (PVA).
Miscellaneous thickeners:
• Gelatin used as a suspending agent and a viscosity increasing
agent
11/9/2022 BA-FP-JU-C

18. Preservation of a suspension
• Water is the most common source of microbial
contamination.
• Also the naturally occurring additives such as acacia
and tragacanth may be sources of microbes and
spores.
• Preservative action may be diminished because of
adsorption of the preservative onto solid particles of
drug, or interaction with suspending agents.
• Useful preservatives in extemporaneous preparations
include chloroform water, benzoic acid and
hydroxybenzoates.
11/9/2022 BA-FP-JU-C

19. Formulation of suspension
1. Control particle size. On a small scale. this can be
done using a mortar and pestle. to grind down
ingredients to a fine powder.
2. Use a thickening agent to increase viscosity of
vehicle by using suspending or viscosity-increasing
agents.
3. Use a wetting agent.
11/9/2022 BA-FP-JU-C

20. The dispensing of suspensions
Method of preparation
A. Crystalline and granular solids are finely
powdered in the mortar. The suspending agent
should then be added and mixed thoroughly in
the mortar. Avoid gumming or caking.
B. Gradual addition of vehicle, make a paste then
continue till become smooth and pourable,
rinse and up to volume in a tared bottle.
11/9/2022 BA-FP-JU-C

21. Variations:
• If wetting agents are included in the formulation, add
them before forming the paste.
• If syrup and/or glycerol are in the formulation, use this
rather than water to form the initial paste.
• If soluble solids are being used, dissolve them in the
vehicle before or after making the paste.
• Leave addition of volatile components, colourings or
concentrated flavouring tinctures such as chloroform
spirit, liquid liquorice extract and compound tartrazine
solution until near the end.
11/9/2022 BA-FP-JU-C
The dispensing of suspensions

22. Preparation of suspension from oral solid
dosage form
• The tablet will be crushed or capsule contents emptied
into the mortar and a suspending agent added.
• A paste is formed with the vehicle and then diluted to a
suitable volume, with the addition any other desired
ingredients such as preservative or flavour.
• A short expiry of no more than 2 weeks (more likely to
be 7 days) should be given owing to the lack of
knowledge about the stability of the formulation.
11/9/2022 BA-FP-JU-C

23. Preparation of suspension from dry powders
and granules for reconstitution
• Reconstitution because of chemical or physical
instability.
• Loosening of powder from bottom of the container.
• The specified amount of cold, purified water should
then be added, sometimes in two or more portions
with shaking.
• some preparations may be prepared immediately
before taking from individually packed sachets of
powder or from bulk solids.
11/9/2022 BA-FP-JU-C

24. Containers for suspension
• Suspensions should be packed in amber bottles,
plain for internal use and ribbed for external use.
• There should be adequate air space above the
liquid to allow shaking and ease of pouring.
• A 5 mL medicine spoon or oral syringe and
measuring cup should be given when the
suspension is for oral use.
11/9/2022 BA-FP-JU-C

25. Special label and advice for suspension
• The most important additional label for suspensions is
'Shake well before use',
• Store in a cool place. Stability of suspensions may
be adversely affected by both extremes and variations
of temperature.
• Some suspensions. such as those made from
reconstituting dry powders, may need to be stored in a
refrigerator.
• Extemporaneously prepared and reconstituted are
required to be recently or freshly prepared, with a 1-4-
week expiry date.
11/9/2022 BA-FP-JU-C

26. 200ml Calamine Lotion BP
Master formula 200ml
Calamine 15g 30g
Zinc oxide 5g 10g
Bentonite 3g 6g
Sodium citrate 500mg 1g
Liquified phenol 0.5ml 1ml
Glycerol 5ml 10ml
Water to 100ml to 200ml
11/9/2022 BA-FP-JU-C

27. Key points
• Suspensions can be used to administer an
insoluble solid by the oral route.
• Suspensions may be used to replace tablets, to
improve dissolution rate, to prolong action and to
mask a bad taste.
• Solids may be diffusible or indiffusible and require
different dispensing techniques.
• Stokes' equation can be applied when formulating
a suspension to help ensure accurate dosage of
the drug.
• Flocculated particles settle quickly and redisperse
easily, whilst deflocculated particles settle slowly
but tend to cake.
11/9/2022 BA-FP-JU-C

28. Key points
• Hydrophobic solids may require wetting agents.
• Suspending agents are added to slow down the
rate of settling of the solid.
• Suspending agents may be natural
polysaccharides, semi synthetic polysaccharides,
clays or synthetic polymers.
• Some suspensions are made by adding water to
reconstitute manufactured powders when
stability is a problem.
• Shake well before use' and 'Store in a cool place‘
should be part of the labels on a suspension.
• Inhalations are suspensions of a volatile material
adsorbed onto a diffusible solid.
11/9/2022 BA-FP-JU-C