In the pharmaceutical industry, polymorphism control of an active pharmaceutical ingredient (API) is critical since polymorphs have different chemical and physical stability, solubility, morphology, and hygroscopicity. During the manufacturing process, it is often required to convert a less stable form to a more stable form.
This work describes the development of a polymorph transformation process to convert a monohydrate (A) to a neat form (B) of an API (X). Discussions will be focused on three aspect: (1) strategy for solvent selection, which was driven by thermodynamic boundary and practical considerations; (2) kinetics for the form transformation, in particular, its dependence on temperature and solvent composition; (3) Effect of solvent composition and temperature on particle size and morphology. In this work, an integrated crystallizer equipped with Lasentec, Raman, and temperature probes was used to allow real -time monitoring of the crystal size and form, which offers great advantage of quantitative characterization of the polymorph transformation process.
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