Pomalidomide Dihydrate Crystalline Form Stability

The patent applies parameter changes by discovering and characterizing multiple polymorphic forms of pomalidomide (Forms I, II, III, and solvates including hydrates and acetone solvate), each with distinct crystal structures and physical properties. These different solid forms exhibit varying solubility, dissolution rates, and stability characteristics, allowing selection of the optimal form for improved bioavailability while maintaining manufacturability through established crystallization and formulation techniques.

The patent utilizes phase transitions by providing multiple crystalline polymorphic forms of pomalidomide that can be selectively obtained through controlled crystallization from different solvents and conditions. Each polymorphic form represents a distinct solid phase with unique stability and dissolution characteristics, enabling optimization between physical stability and dissolution rate by selecting the appropriate crystal form for the specific application.

The patent applies parameter changes by identifying and characterizing four distinct polymorphic forms and multiple solvates of pomalidomide, each with different crystal packing arrangements, hydrogen bonding patterns, and molecular conformations. These structural parameter variations result in different solubility and dissolution behaviors, allowing selection of the most suitable crystalline form to achieve both adequate stability and dissolution performance.