(194f) Selection and Development of a De-Solvated Solid Form for An Active Pharmaceutical Ingredient

In the development of active pharmaceutical ingredient (API), solid form screen and selection are key initial development activities to identify and select a suitable development solid form for subsequent manufacturing and formulation activities. The solid state information obtained in the early stage of development not only contributes to the solid form selection but also facilitates the subsequent crystallization development to produce the selected form with the desired properties. This presentation provides an example with the development for a BI compound.

For this BI compound, a de-solvated form of was identified and selected as the development form due to its superior solubility and stability compared to other forms identified. The compound has strong tendency to form solvates with various solvent systems. The selected form, Form I, was originally obtained from de-solvation during the solid form screening. Several crystallization attempts, including direct crystallization, slurrying and desolvation, were conducted to identify the best pathway to produce Form I. In comparison, de-solvation was identified to be the most straightforward method to produce Form I. A process was successfully developed to produce Form I with high quality in the kg scale. In this process, a suitable solvate, identified with the information found in the early polymorphism study, was first produced by solution crystallization followed by drying for the conversion to Form I. This presentation will cover the details on how this process was developed to produce this challenging solid form, including how the starting solvate was identified, kinetic studies of the form conversion by inline mass spectrometer and optimization of the process to further improve the scalability and manufacturability, etc.