Development of ASD Formulation for Clinical Studies – From Amorphous Theoretical Solubility Calculation to ASD Tablet Development

Amorphous formulation becomes an attractive strategy to deliver poorly water soluble drugs owing to its higher solubility. This presentation will cover three major topics for amorphous drug product development to support clinical studies – (1) theoretical solubility calculation for amorphous drugs; (2) effect of ASD composition on the disintegration and drug release of ASD tablets; (3) a case study of developing an ASD formulation to improve bioavailability and mitigate mechanical instability risk of crystalline form for early phase clinical studies. The first topic will discuss different methods of calculating amorphous drug solubility and the experimental evaluation of these equations. Based on the evaluation, one calculation equation was recommended based on the overall accuracy and complexity. The validated amorphous solubility calculation provides a guidance for ASD composition screening and developing ASD formulation. To successfully apply ASD formulation in clinics, final dosage form (e.g. ASD tablets) is usually needed. Owing to great amount of polymers in the ASD composition, the disintegration and drug release usually become an issue for ASD tablets especially when ASD loading increases. The second topic will discuss how polymer type, ASD loading in tablet and polymer-drug ratio affect the disintegration and drug release of ASD tablets. At last, the third topic will present a case study of developing an ASD tablet, guided by amorphous solubility calculation, to improve the drug bioavailability and mitigate mechanical instability risk of the selected crystalline form. To summarize, the overall goal of this presentation is to provide an industrial perspective for the design and formulation of amorphous drug products based on fundamental understanding of amorphous materials.

Wei Zhang, Principal Scientist, Small Molecule Pharmaceutics , Genentech