Mechanisms of Dissolution of Fast Release Solid Dispersions

Abstract

Drug dissolution from a solid dispersion is dependent on the technology employed to prepare the dispersion and on the proportion and properties of the carrier used. The diffusion models describing dissolution from multi-component solids seem to adequately describe drug release from non-disintegrating systems in the weight fraction range where the drug phase is expected to control dissolution. When solid dispersions have higher dissolution rates than corresponding mechanical mixtures, solid state changes during the formation of the dispersion are indicated. These increases in rate may result from the formation of higher energy phases of either component or from interactions between the components. The carrier may play an important role in the formation of these phases and in stabilizing them during subsequent dissolution. When a large relative solubility difference exists between the carrier and the drug, deviations from theory can be expected to occur at high carrier weight fractions. The model fails because insufficient drug phase is present to form a viable surface drug layer. Drug release then becomes controlled by dissolution of the carrier. In polymer based systems the presence of drug retards dissolution of the carrier, possibly through effects on binding and polymer swelling. These effects need to be quantified in order to allow prediction of drug release from high carrier weight fraction systems.