MECHANISTIC STUDY ON THE INFLUENCE OF POLYMERS ON SUPERSATURATION MAINTENANCE OF AMORPHOUS SOLID DISPERSIONS DURING DISSOLUTION

Abstract

Amorphous solid dispersions have been widely explored in the pharmaceutical industry to improve the oral absorption of poorly soluble drugs. However, the mechanistic role that polymers play in maintaining drug supersaturation and in the dissolution behaviors of amorphous solid dispersions is still not fully understood. Selection of polymeric additives is still largely based on empirical approaches. In this research work, the supersaturation maintenance ability of polymers in relation to their physicochemical properties was first established using cellulosic based polymers. The use of solubility parameter and Flory-Huggins interaction parameter was also explored as predictive tools to determine the ability of a polymer in inhibiting drug precipitation from supersaturated solutions. Lastly, a mechanistic approach was employed to understand the drug release kinetics and the subsequent maintenance of drug supersaturation from amorphous solid dispersions during dissolution. Several physicochemical properties such as drug-polymer interaction, hydrophilicity of polymer and polymer precipitation inhibition capability were studied. Overall, the developed predictive tools and the understanding on the physicochemical properties influencing the amorphous solid dispersion dissolution will help provide a systematic rationale in the selection of effective polymers during formulation development.