[Crystalline modifications and polymorphism changes during drug manufacture].
More than half of the pharmaceutical compounds exhibit polymorphism or pseudopolymorphism, e.g., they exist as more than one crystalline structure (true polymorphs, hydrates, solvates) or as more or less amorphous products. As such, they show at the solid state different physicochemical properties (melting point, transition point, plasticity, solubility, hygroscopicity, chemical reactivity), which in turn may affect the technological and biopharmaceutical properties of active ingredients or excipients (compactibility, dissolution rate, bioavailability, pharmacological activity, stability). When considering a chemically well-defined compound, one may find one or another crystalline state or polymorphic form according to the source or batch considered. One may also observe changes in technological or biopharmaceutical properties that are due to polymorphic transformations arising from the mechanical or heat treatment or from the environmental conditions (solvent-mediated reactions, desolvation) undergone by the product or the dosage form. The present article presents the fundamental aspects related to the above-mentioned phenomena and reviews both classical and recent examples from the literature reporting transformations during milling or grinding, tabletting, preparation of drug suspensions, granulation, dissolution or release tests, stability trials, spray drying, freeze-drying or preparation of adsorbates or complexes.
Doelker
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Laboratoire de pharmacie galénique, Section de pharmacie, Université de Genève, Quai Ernest-Ansermet 30, CH-1211 Genève 4, Switzerland.
D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004339:Drug Compounding; D004345:Drug Industry; D007536:Isomerism; D004364:Pharmaceutical Preparations / Q000737:chemistry*
D004364:Pharmaceutical Preparations
Modifications cristallines et transformations polymorphes au cours des opérations galéniques.