In vitro release studies on drugs suspended in non-polar media I. Release of sodium chloride from suspensions in liquid paraffin

Abstract

The release of a readily water-soluble substance (sodium chloride) from a liquid paraffin phase to an underlying water phase was investigated as a function of particle size (10–50 μm) and concentration (up to 10% m/m). Transport of the suspended particles to the interface by sedimentation was the rate limiting step. The release rate increased with primary particle size and concentration. The small particles showed a more pronounced concentration dependence than the large ones. During settling, agglomerates were formed. But, mild shear rates kept the primary particles in the deglomerated state. Low concentrations of DOSS-Na (di(2-ethylhexyl) sodium sulphosuccinate) up to 0.2% m/m in liquid paraffin reduced the degree of agglomeration, while trace amounts of water (0.01 and 0.05% m/m) showed the opposite effect. The observed phenomena are discussed on basis of the DLVO-theory, supplemented with considerations about forces due to gravity, shear and liquid bridge formation, and the kinetics of agglomeration.