Microelectrophoretic Studies of Aqueous Auspension Systems of Pharmaceutical Interest

Abstract

The relationship between electrophoretic properties and suspension characteristics has been studied, A monodisperse polystyrene latex dispersion was used as a model system, the results found from this have been applied qualitatively, and where possible quantitatively, to suspensions of the drugs Betamethasone, Griseofulvin, Nalidixic Acid and Thiabendazole. The effect of adding anionic (sodium alkyl sulphates), cationic (alkyl trimethylammonium bromides) and non-ionic (polyoxyethylene glycol monoethers of n alkanols) surface active agents, and mixtures of these ionic and non-ionic species, on the electrophoretic properties of the above dispersions has been measured, and the results correlated with sedimentation volume studies of the drug suspensions. Mobility versus pH plots for the drugs showed that the charge on the particle varied with pH, suggesting the advisability of this sort of study before formulation, The non-ionic surfactants are adsorbed in a looped monolayer as was shown by a plateau region in the mobility versus pH plot, these non-ionic surfactants were effective as steric stabilizers in preventing suspension caking. With cationic surfactants adsorption is a two stage process characterized by neutralization of negative charge followed by charge reversal, The free energy of adsorption was measured and depended on alkyl chain length, the driving force for adsorption being the hydrophobic effect. Displacement of the reversal of charge concentration by non-ionic surfactant depended on its concentration and the type of cationic surfactant, Adsorption of anionic surface active agents caused an increase in zeta potential, An estimate of the free energy of adsorption was made from the slope of the zeta potential versus logy concentration surfactant plot. The zeta potentials found with varying concentration of anionic surfactant were used to calculate the DLVO potential energy plot for the Thiabendazole/sodium dodecyl] sulphate system. Added non-ionic surface active agents were found to complex with anionics, complexation being dependent on ethylene oxide chain length. From sedimentation volume studies the existence of coagulated, deflocculated and secondary minimum flocculated systems is discussed and correlated with zeta potential measurements, The concept of controlled flocculation, or perhaps more correctly controlled coagulation, as a means of preparing a stable pharmaceutical suspension, is supported, It is concluded that there is need for revision in the terminology describing coarse suspension systems, most suspensions described as flocculated being in fact coagulated,