Utilization of DSC for Pharmaceutical crystal form quantitation

Abstract

The existence of multiple crystal forms in a drug substance poses interesting development challenges as the material is taken from discovery through formulation, manufacture and market. There are a number of factors why drug substances under development are screened for presence of multiple crystal forms. Different crystal forms may exhibit varied performance properties including bioavailability and solubility, as well as, differences in physical properties such as morphology and melting point. These properties can affect the design of the manufacturing processes for the bulk drug substance, the formulation and the performance of the drug product. This paper will focus on the application of differential scanning calorimetry (DSC) for the quantitation of pharmaceutical crystal forms. Feasibility studies were conducted on several pharmaceutical drug substances which were known to have multiple crystal forms, to determine if quantitative, semi-quantitative or limit of detection tests could be developed. The conclusion from these studies is that polymorphic crystal systems comprised of either close, or melting with decomposing, endotherms, competing transitions, or that contain sample contaminants, may not be optimum candidates for quantitation by DSC. Conversely, crystal systems that contain polymorphs that exhibit well-resolved endothermic or exothermic transitions, for either solvated vs. unsolvated species or both unsolvated, may be excellent candidates for crystal form quantitation by DSC.