Physico-chemical characterisation of the modifications I and II of (R,S) propranolol hydrochloride: solubility and dissolution studies

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• 作者：Bartolomei ; Monica ; Bertocchi ; Paola ; Cotta Ramusino ; Marina ; Santucci ; Nora ; Valvo ; Luisa
• 关键词：Propranolol hydrochloride ; Polymorphism ; Infrared spectroscopy ; Physical stability ; Equilibrium solubility ; Intrinsic dissolution
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：1999
• 出版时间：November 1, 1999
• 年：1999
• 卷：21
• 期：2
• 页码：299-309
• 全文大小：158 K

文摘

The crystallisation conditions and the physicochemical properties of the modifications I and II of (R,S) propranolol hydrochloride were investigated. Detailed methods of preparation of the two forms were described. Data from FTIR spectroscopy, X-ray powder diffraction, thermal analysis, solubility and dissolution studies were used for the identification and the characterisation of the two forms. The forms I and II were easily differentiated by their IR spectra, X-ray patterns and thermal behaviour. The two polymorphs were found to be enantiotropically related to each other. Their stability was followed at room temperature over a period of 1 year and under different conditions of temperature, grinding and compression to verify the tendency to solid–solid transition and to study the existence range of the two forms. The equilibrium solubilities of the two polymorphs in n-octanol were determined as well as their dissolution profiles as pellets in aqueous medium. These studies showed that form I, the less thermodynamically stable, was more soluble (by more than 34 % ) and dissolved faster than form II in agreement with the thermodynamic rules (A. Burger, R. Ramberger, Mikrochim. Acta II (1979) 259–271).