Controlled Release as a Strategy to Prevent Solution-mediated Phase Transformation in Amorphous Solid Dispersions: Effect of Dosage Form Design

The purpose of this study was to define the limits of developing a controlled-release amorphous solid dispersion (CRSD) system intended for enhancing the bioavailability of poorly water soluble drugs. Feasibility of multiple solid oral CRSD dosage form designs, such as spray dried powders, coated beads and compressed matrices (dry granulations and tablets) was evaluated. Solid dispersion powders were characterized in terms of ability to establish and maintain amorphicity in the dry form (by DSC and XRD) and ability to circumvent events leading to solution-mediated phase transformation (SMPT), or recrystallization during dissolution. While all dosage forms could successfully be produced with the amorphous dispersion, great differences in dissolution/recrystallization profiles were found, depending on how the controlled release agent was incorporated. These studies reveal that when designing a solid dispersion system, greater benefit can be derived by selecting the appropriate dosage form design, granting the formulator the much sought-after control over the challenge of SMPT.M.Sc.2018-01-05 00:00:0