Improving the properties of active pharmaceutical ingredients by polymorph, salt and cocrystal screening
Solids exist as crystals, amorphous or subcooled liquids. The degree of crystallinity determines the long range order in a solid phase. Molecules when transferred from the solution to the solid phase may take many different crystal forms (polymorphs, solvates/hydrates, salts, co-crystals). Theoretically, there are 230 space groups describing the diversity of a crystalline material. About two thirds of pharmaceutical small molecules exist in more than one polymorphic solid form. Crystallization of polymorphs still has a touch of art. Various solid forms often display different mechanical, thermal, physical and chemical properties that can influence the bioavailability, hygroscopicity, stability and other performance characteristics of an API. The goal of this project is to unravel the inter- and intra-molecular forces that are responsible for the molecular packing, conformational polymorphism, and salt/cocrystal formation and therefore, predict and screen possible polymorphs, salts and cocrystals of a given API. This will be achieved by performing high-throughput experimentation to guarantee a product with desirable solubility, dissolution rate, and stability.