Development of an Amorphous Solid Dispersion Formulation for Mitigating Mechanical Instability of Crystalline Form and Improving Bioavailability for Early Phase Clinical Studies

• Published in: Molecular pharmaceutics Vol. 20; no. 5; pp. 2452 - 2464
• Main Authors: Chiang, Cheng W., Lubach, Joseph W., Chen, Tao, Chin, Steven, Ly, Justin, Zhang, Wei, Hou, Hao Helen, Nagapudi, Karthik
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.05.2023
• Subjects: Animals; Biological Availability; Dogs; Drug Liberation; Excipients - chemistry; Polymers - chemistry; Sodium Dodecyl Sulfate - chemistry; Solubility; Tablets - chemistry; ASD tablet; mechanical instability; bioavailability; formulation development; amorphous solid dispersion (ASD)

In this work, an amorphous solid dispersion (ASD) formulation was systematically developed to simultaneously enhance bioavailability and mitigate the mechanical instability risk of the selected crystalline form of a development drug candidate, GDC-0334. The amorphous solubility advantage calculation...