Suspensions Flashcards
Definition of a suspension
Suspension: Dispersion of finely divided solid particles in a liquid medium
- -> Coarse suspension (particles > 1 micron)
- -> Colloidal suspension (particles <= 1 micron)
- -> Liquid medium can be aq/non-aq
Applications of a suspension
1) For oral use
- Provide mean to administer insoluble solids in liquid form
- Provide mean to supply distasteful drugs in a form pleasant to taste
- Provide mean to administer insoluble compounds for their absorptive/antacid properties in the treatment of gastric disorders
2) For injection
- Provide mean of sustaining drug release as in depot therapy
3) For external use
- Provide mean to apply insoluble drugs to skin
Desirable properties of a suspension
- Chemically stable
- Low rate of particle sedimentation (If high, wont have uniform distribution of drug particles)
- Particles should be readily redispersed upon gentle shaking of container
- Particle size should remain fairly constant throughout storage (Affects rate of dissolution)
- (For external use) Should spread easily & yet not so mobile that they run off
Flow (Preferably: Thixotrophy - Shear thinning, slow recovery of apparent viscosity upon standing)
- Should pour readily from container
- Suspensions should flow readily from container
Factors affecting rate of sedimentation of particles
Stokes equation: [2r^2 (p1-p2) g] / 9n
–> Though does not apply precisely to usual pharm suspension, factors expressed in eqn can be used to modify rate of sedimentation of particles
1) Radius of particle (Increase, incr sedimentation)
2) Viscosity (Increase, decr sedimentation)
What are floccules?
Aggregates of particles
Is flocculated/deflocculated suspension preferred?
Flocculated
Properties of flocculated suspension
Nature of dispersed phase: Aggregates
Sedimentation rate: Rapid
Nature of final sediment:
- A porous sediment forms on prolonged standing
- Relatively large vol
- Easy to redisperse
Nature of supernatant liquid: Clear
Rheological property of conc suspension:
- Plastic flow with thixotrophy
How to determine degree of flocculation?
1) Allow suspension to stand until vol of sediments b/c a constant (Vt)
2) Centrifuge the suspension & determine the resultant vol of sediments (Vc)
3) Determine ratio of Vt & Vc
- -> Greater ratio, greater flocculation
What is included in the formulation of a suspension?
- Dispersed phase
- Liquid vehicle
- Wetting agent
- Flocculating agent
- Thickening agent
- pH buffer
- Preservative
- Colorant, favour & fragrance
Dispersed phase (What, types)
What: Consists of insoluble solid particles
(Also known as suspensoid)
Types:
(i) Lyophilic solids
- Solvent-loving; wetting agent not required
- May also increase viscosity of the suspension
(ii) Lyophobic solids
- Not solvent-loving, require wetting agent for dispersion in the liquid vehicle
- Most drugs are hydrophobic
Liquid medium (What, types)
What: Also known as dispersion medium/continuous phase
- May be aq/non-aq
Wetting agent (Function, types)
Function: Make solid particles more penetrable by dispersion medium
Modes of action:
(i) Reduce solid-liquid interfacial tension
(ii) Imparts hydrophilicity to particle surface
- Usually pre-mixed with the solid particles in the preparation of the suspension
Eg. of wetting agents for aqueous dispersion medium:
1) Surfactants (Spans with HLB 7-9)
- Used at conc below cmc
2) Hydrophilic polymers (Eg, acacia, xanthan gum)
3) Polyhydric alcohols (Eg. glycerin, polyethylene glycols)
- To impart hydrophilicity
[NOTE: Diethylene glycol is TOXIC]
Flocculating agents (Types, examples)
1) Electrolytes (Eg. salts like NaCl)
- Affects zeta potential which governs interparticulate replusion/attraction
Dependent on:
i) Concentration of electrolytes
Low (0.01-1%) [Favourable]:
- Generally sufficient to reduce zeta potential to <
critical value for interparticulate attraction
- vdW attractive forces cause solid particles to form flocs
- on prolonged standing, flocs will settle to form porous sediment that is easy to redisperse
(Flocculated suspension)
High: Reverse sign of zeta potential to cause repulsion
- on prolonged standing, particles will settle to form compact sediment (Deflocculated suspension)
ii) Valency of electrolytes
- Monovalent ions sufficient to induce flocculation of weakly charged particles
2) Surface active agents
i) Ionic agents
- Behave like electrolytes (but bigger), similar mechanism to induce flocculation
ii) Non-ionic agents
- Used at conc > cmc for flocculating agents
- Micelles are adsorbed at surface of particles, serving as bridges between particles to bring about flocculation
3) Hydrophillic polymers (Eg. acacia, alginates, tragacanth)
Low conc (<0.05%): Sufficient to bring about flocculation - Adsorbed at surface of particles, serve as bridges
High conc (0.05-0.1%): Protective colloid effect - Polymers form protective coat, separating particles from one another
High conc (>0.1%): Viscosity enhancing effect - Polymers increase viscosity, reducing flowability of the suspension
Thickening agent (Function, examples)
Function: To assist in the suspension of solid particles through thickening of the dispersion medium
Eg. gums, gelatin, bentonite, carboxymethyl cellulose, polyvinylpyrrolidone
Depending on CONCENTRATION used, hydrophilic polymer may exert other effects
< 0.05%: Flocculating effect
0.05-0.1%: Protective colloid effect
> 0.1%: Viscosity-enhancing effect
Purpose of pH buffers
- To provide optimal stability of suspension
- Indiscriminate use should be avoided
