Susan M Reutzel-Edens | PubMed Health

PubMed2006

Achieving polymorph selectivity in the crystallization of pharmaceutical solids: basic considerations and recent advances.

Controlling the appearance of crystal polymorphs of pharmaceuticals is essential in developing robust large-scale crystallization processes in the pharmaceutical industry. This review describes many of the thermodynamic and kinetic factors that are important for controlling crystal polymorphism and discusses recent advances in the understanding of the molecular mechanisms of polymorph appearance. Case studies in the development of crystallization processes of pharmaceutical solids, where process analytical technology was applied to resolve the complexities introduced by crystal polymorphism, are discussed.

Crystallization↗

PubMed2003

Crystal forms of LY334370 HCl: isolation, solid-state characterization, and physicochemical properties.

LY334370 HCl, a 5HT1f agonist investigated for the treatment of migraines, was identified in five crystal forms: three anhydrates (I-III), a dihydrate, and an acetic acid solvate. The identification and characterization of these crystal forms by optical microscopy, differential scanning calorimetry, thermogravimetric and moisture sorption analyses, solid-state NMR spectroscopy, and X-ray crystallography (Form I only) are presented. Physical properties, including hygroscopicity, solubility, and intrinsic dissolution rate, were assessed for Form I and the dihydrate, the two most viable crystal forms for commercial development. Surprisingly, anhydrous Form I was found to be the thermodynamically most stable crystal form in water, dissolving six times slower than the dihydrate, a difference that correlates well with the rank order of aqueous solubility.

Benzamides↗