Suspension Formulation & Stability (PDF)

Introduction » A coarse dispersion in which insoluble particles, generally greater than | um in diameter, are dispersed in a liquid medium, usually aqueous. » Useful for administering an insoluble or poorly soluble drug. * May be used for oral, parenteral, and ophthalmic, and dermato...

Introduction » A coarse dispersion in which insoluble particles, generally greater than | um in diameter, are dispersed in a liquid medium, usually aqueous. » Useful for administering an insoluble or poorly soluble drug. * May be used for oral, parenteral, and ophthalmic, and dermatological uses. » Suspension vs. colloids.  Desirable Criteria I. The suspended material should not settle too rapidly; 2. The particles that do settle to the bottom of the container must not form a hard cake 3. Should be readily dispersed into a uniform mixture when the container is shaken. 4. Must not be too viscous to pour freely from the bottle or to flow through a syringe needle.  Pharmaceutical Applications of Suspensions ¢ Oral » Topical (skin or mucous membranes) * Parenteral (injection) Pulmonary (inhalation)  Suspensions as oral drug delivery systems « Difficulty in swallowing solid dosage forms » The adsorption of toxins (kaolin) magnesium carbonate and magnesium trisilicate (neutralize excess acidity). » The taste of the drugs (paracetamol sol.Vs. susp) / chloramphenicol vs. chloramphenicol palmitate.  Suspensions for topical administration * Fluid preparations (calamine lotion, deposit after solvent volatilization). » Semisolid (pastes, high concentrations of powders). * In an emulsion base (zinc oxide creams). Suspensions for parenteral use and inhalation therapy » The duration of activity can be controlled (PS. — Dissolution rate — absorption). » Suspension in oil (inj.) — oil globule — | SA — | dissolution rate — controlled absorption. (oil vs. aqueous). Suspensions for parenteral use and inhalation therapy * Vaccines — killed microorganisms (Cholera) / toxoids adsorbed on to a substrate of aluminium hydroxide or phosphate (Diphtheria and Tetanus) — prolonged antigenic stimulus — high antibody titre » X-ray contrast media (Barium sulphate / oral or rectal).  Stability of Suspensions. Solubility Aspects * If water — ™ degradation — suspension — stability (vs. solution). » Insoluble derivative of soluble > drug suspension (oxytetracycline hydrochloride vS. oxytetracycline). » Pd for reconstitution — * stability (amoxicillin). » Non aq. Vehicle (fractionated coconut oil). Il. Steric stabilization of suspensions * Pharmaceutical suspensions may be stabilized against coagulation by adding materials that form adsorbed layers around the particles so that the approach of their surfaces and aggregation to the coagulated state is hindered. dispersant —y soluble tails anchoring ufi%éj—\/ groups adsorption O —— naked particle stabilised particle |l. Steric stabilization of suspensions * Natural (gum tragacanth) and synthetic (non-ionic surfactants and cellulose polymers). » These materials may increase the viscosity of the aqueous vehicle and thus slow the rate of sedimentation of the particles.  l1l. Caking and Flocculation * Upon sedimentation — lower particle pressed — | repulsive barrier — close packing — formation of bridges between the particles — caking * Addition of electrolyte — accumulation of charges — loose bonding between particles (flocculates / floes). l1l. Caking and Flocculation Deflocculated & ~ Flocculated suspension /  l1l. Caking and Flocculation Flocculated Non-flocculated. Particles forms loose 1. Particles exist as separate entities aggregates and form a network like structure. Rate of sedimentation is high 2. Rate of sedimentation is slow. Sediment is rapidly formed 3. Sediment is slowly formed W. Sediment is loosely packed 4. Sediment is very closely packed and doesn’t form a hard cake and a hard cake is formed. Sediment is easy to redisperse 5. Sediment is difficult to redisperse W. Suspension is not pleasing in 6. Suspension is pleasing in appearance appearance. The floccules stick to the 7. They don’t stick to the sides of the sides of the bottle bottle  IV. Rheology of suspensions * Low shear rates — * viscosity — | sedimentation — 1 stability. » High shear rates (shaking) — | viscosity —> easy administration. » Flocculated systems - plastic or pseudoplastic flow. » Deflocculated systems > Newtonian flow.  Formulation of suspensions l. Particle Size Control * Small PS. — | Sedimentation rate. *PS.> 5 pm — grittiness * PS.> 25 pym — blocking syringe needle ¢ PS. controls dissolution rate.  Formulation of suspensions Il.Wetting Agents Most insoluble solids exhibit varying degrees of hydrophobicity — not be easily wetted — large porous clumps / remain on the surface. » The solid / liquid interfacial tension must be reduced (Surface-active agents, HLB 7 -9). » Tweens and spans for oral use ( The addition of an inorganic electrolyte to an aqueous suspension will alter the zetapotential of the dispersed particles and, if this value is lowered sufficiently, flocculation may occur.  Formulation of suspensions V. Flocculating agents e Surfactants: »lonic surface-active agents may also cause flocculation. »Non-ionic surfactants may forming a loose flocculated structure (adsorb on tomore than one particle).  Formulation of suspensions V. Flocculating agents » Polymeric flocculating agents: »Polymers (starch, alginates, cellulose derivatives, tragacanth, carbomers and silicates) — linear branched-chain molecules — gel-like network within the system / adsorbed on to the surfaces of the dispersed particles — holding them in a flocculated state.. Any Questions?