By Samuel kyeremateng, Ph.D.
AbbVie, North Chicago, IL
Small molecule solid dosage drug product with the drug in the crystalline state is typically preferred due its more desirable properties including stability, purity, and ease of manufacture. However, the percentage of drug candidates with poor aqueous solubility emerging from drug discovery is steadily increasing with properties beyond the “rule of five” (bRo5). This presents a significant challenge to achieve acceptable bioavailability during drug product development. Mitigation strategies including crystal structure modification and particle size reduction are often considered. Another strategy involves transforming the crystalline drug into the amorphous form and embedding it in a polymer matrix, a technique commonly referred to as amorphous solid dispersion (ASD). The approach has an inherent risk of the amorphous drug reverting to the crystalline form during dissolution or within the shelf-life if the drug product is not adequately designed. In this presentation, key considerations in terms of ASD drug product design and manufacturing will be highlighted. Furthermore, application of modeling techniques to support design, development, and manufacturing of ASDs shall be discussed.