title: Polymorph screening of an active material.
abstract: Polymorph screening is currently one of the most important tasks for innovators and for generic companies from both pharmaceutical and intellectual property rights aspects. The different polymorphs have different physicochemical properties, such as the crystal polymorph-dependent solubility which influences the bioavailability. A former drug candidate obtained from Sanofi Pharmaceutical Company (Hungary) was investigated to explore its polymorphism, to distinguish the morphologies generated by analytical examinations and to investigate their relative stabilities. An Avantium Crystal 16 automatic laboratory reactor system was used for the polymorph studies and the studies of their dissolution. Eight polymorphs were obtained by crystallization and transformation methods then characterized by XRPD, DSC, and Raman spectroscopy, scanning electron microscopy, and light microscopy. All the morphologies could be stored in solid without any form transformation for a long time (2 years investigated). According to the first relative stability results, Form I, III, IVa, V, VI, VII are unambiguously metastable forms. Form II and IVb have similar thermodynamic stabilities, that were higher than those of the other polymorphs. A special dissolution medium was developed in which the eight polymorphs showed clear differences in the rate of dissolution.
authors.affiliation: University of Szeged, Department of Pharmaceutical Technology, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Láng
authors.forename: V
authors.initials: V
authors.lastname: Kiss
authors.forename: R
authors.initials: R
authors.lastname: Ambrus
authors.forename: G
authors.initials: G
authors.lastname: Farkas
authors.forename: P
authors.initials: P
authors.lastname: Szabó-Révész
authors.forename: Z
authors.initials: Z
authors.lastname: Aigner
authors.forename: E
authors.initials: E
authors.lastname: Várkonyi
mesh_terms: D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D013059:Spectrum Analysis, Raman / Q000379:methods; D013816:Thermodynamics; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations
keywords: Dissolution test; Drug candidate; Polymorph; Relative stability