Formulation Development of Amorphous Dispersions

This chapter examines the development of clinical and commercial formulations of amorphous dispersions. It considers the various means available to render a crystalline drug amorphous. The chapter explores the downstream ramifications of each technique, such as on the dosage forms available, and special processing and handling. It gives the high-level strategic picture of amorphous formulation development, a process that best fits the framework of quality by design (QbD) advocated for by the FDA. The chapter reviews a detailed case study of the first amorphous dispersion-based drugs developed and commercialized inhouse, the hepatitis C protease inhibitor VX-950 or telaprevir (Incivek). It focuses on developing a drug product manufacturing process, including defining parameters, developing the design space, modeling, and applying the QbD framework to manufacture. The chapter examines the analytical methods used to discriminate dispersion attributes and tablet properties that could affect performance of the product in the clinic. Keywords: amorphous dispersions; drug product manufacturing process; quality by design (QbD); telaprevir