282799 Impact of a Reversible Solid State Form Change On Particle Morphology and Bulk Powder Properties of a Pharmaceutical Compound
For efficient formulation processing of a pharmaceutical drug product, it is desirable to have an active pharmaceutical ingredient (API) that handles well in terms of flow and bulk density, especially for products with high drug loadings. To improve bulk API powder property behavior, particle engineering techniques can be employed during the crystallization step to alter the morphology of the API crystals from needles, which normally have poor flowing powders, to bricks or rods. Although particle engineering can have a significant impact on particle morphology, the susceptibility of the API to crystalline form change from environmental factors such as relative humidity must also be carefully studied and controlled.
A case study is presented for Compound A whose thermodynamically desired crystalline form has an undesired morphology but can be modified to bricks or rods through a particle engineering approach. Compound A is known to crystallize as iso-structural solvates (Form I) in all solvent systems that have been studied. Upon isolation and drying, Form I desolvates to Form II which can reversibly convert to Form III in the solid state at a critical relative humidity. In this presentation, the crystal structures of Forms I, II and III will be discussed and used to explain how the form changes impact the integrity and morphology of the API crystal as well as the bulk powder properties. The importance of this work is to gain a fundamental understanding of how the API crystal morphology improvement made during crystallization can be retained in the post crystallization steps of drying, storage and handling. The thorough understanding of the crystal structures can provide valuable insights for handling bulk powders to maintain desired API powder properties for drug product processing.
See more of this Group/Topical: Food, Pharmaceutical & Bioengineering Division - See also TI: Comprehensive Quality by Design in Pharmaceutical Development and Manufacture