Impact of Polymer Composition and Properties on the Dissolution Characteristics Of HPMCAS-Based Spray-Dried Dispersions

For compounds requiring solubilization (i.e., BCS Class II and IV compounds), the concentration profile of dissolved drug affects absorption, which can be increased by making amorphous dispersions (i.e., SDDs) of drug in polymer. Critical performance attributes include

• extent of dissolution,

• rate of dissolution,

• sustainment of dissolved-drug levels, and

• the nature (e.g., activity, dissolution rate) of any precipitate.

Selection of the optimal polymer for the SDD will depend on which of these attributes dominate for a particular active compound or application. The goal of this work was to investigate the impact of the composition and properties of hydroxypropyl methylcellulose acetate succinate (HPMCAS) on the dissolution performance of spray-dried dispersions (SDDs), with the ultimate goal of optimizing in vivo SDD performance. SDDs of three different actives—phenytoin, itraconazole and CP-800,569—and various HPMCAS polymers were spray-dried from a volatile organic solvent. In addition to commercial grades of HPMCAS, custom-synthesized HPMCAS polymers with various substituent levels were used to form SDDs. The dry powder and dissolution properties of the resultant SDDs were then assessed by a variety of methods. Dissolution testing allowed assessment of dissolution rate, the extent of supersaturated drug that could be achieved, and the degree to which these supersaturated drug concentrations were sustained over time.

Bioavailability Enhancement