(340a) Enhanced Dissolution Performance of Amorphous Solid Dispersions By Size Reduction

Amorphous solid dispersions (ASDs) are widely used in pharmaceutical industries in order to enhance the drug absorbance, solubility, dissolution rate. Although the ASDs have higher solubility, the corresponding dissolution rate naturally depends on the nature of the polymeric matrix and particle size. Unfortunately, particle size reduction promotes recrystallization rate, because it increases the available surface areas of the ASDs to environment, both during storage and during exposure to dissolution medium. The effect of particle size on the dissolution behavior of amorphous griseofulvin (GF) particles was investigated using 0-50% Kollidon® VA 64 as a polymeric crystallization inhibitor. Results show that both the final dissolved GF concentration, and the dissolution rate of GF amorphous solid dispersions (ASDs) are inversely proportional to the particle size. The solution concentrations for the smallest (45-75 μm) size group with different polymer loading at 2 hours were 1.5 to 7 and 1.3 to 4 times higher than those for the largest (250-355 μm) group under non-supersaturating and supersaturating conditions, respectively. The dissolution rate of GF ASDs with 50% polymer loading for the finest group was 2.7 times higher than for the largest group under supersaturating conditions. The individual rates of dissolution and recrystallization were assessed through surface concentration and Avrami recrystallization rate kinetics. That indicated that particle size reduction enhanced ASD drug loading by reducing the amount of polymer necessary as finest size ASDs initially dissolve faster negating their higher recrystallization rate. Kollidon® VA 64 at 30% loading was sufficient to inhibit the GF recrystallization. Thus the combination of particle size reduction and recrystallization inhibition is effective for improving the dissolution behavior of GF ASDs.