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abstracts
Polymorphs are compounds with the same chemical composition, however the molecules are arranged in at least two different ways in the solid state. Famotidine is a histamine H2-receptor antagonist inhibitor of gastric secretion and widely used in gastric and duodenal ulcer disease. Two polymorphs are described for famotidine, A and B. The polymorph A is the most thermodynamically stable form and polymorph B is the kinetically favored form being marketed because it presents greater pharmacological activity. The aim of this study was to evaluate the occurrence of famotidine polymorphs in five raw materials acquired from different suppliers. The reference standard (USP) was also analyzed. All samples were characterized by powder X-ray diffraction (PXRD), infrared spectrophotometry (IR-ATR) and differential scanning calorimetry (DSC). PXRD analysis enables us to identify form B in five raw material samples and in the reference standard (USP). However, one of the raw materials additionally shows the presence of polymorphic form A. The DSC and IR-ATR techniques were essential to identify the polymorphic forms of famotidine confirming the results obtained by PXRD. Since the presence of polymorphs can compromise the effectiveness and safety of medicines and there is no official methodology of analysis and control of polymorphism in famotidine raw materials, the polymorphic contamination found in this study are being further analyzed and their physicochemical properties are being evaluated.
abstracts
Polymorphism in solids is a common phenomenon in drugs, which occurs when an active pharmaceutical ingredient shows up in two or more crystalline forms. The polymorphism may influence the physical and chemical properties of pharmaceutical solids, particularly, solubility and dissolution rates which are very important properties because changes in these parameters may affect the absorption and consequently the bioavailability of drugs (especially those that have a low solubility). Carvedilol is an alpha and beta blocking agent that is used for the treatment of various cardiovascular disorders such as angina pectoris, congestive heart failure and hypertension. This work aims to prepare and characterize the forms II and III of Carvedilol drug and compare them in terms of solubility and dissolution rates. Carvedilol raw material was used as source of form II and Form III, and the last is a hemihydrate of Carvedilol that was obtained by a recrystallization process in ethanol/water 1:1 v/v. Both of the crystalline forms have been identified in this study by Powder X-Ray Diffraction experiments and attenuated total reflectance Fourier transform infrared spectroscopy studies demonstrated that the spectra of forms II and III of Carvedilol have no significant differences. The Thermal Analysis curves, as expected, allowed us to discriminate between the two forms due to a hydratation of Form III. In the solubility study, it was found that the polymorphic Form II is more soluble than Form III in certain conditions (pH 1.0 to 7.2). Dissolution studies have shown that polymorphism may influence the quality of Carvedilol tablets, since form III showed a higher drug release after 20 minutes of dissolution testing. Our results suggest that the identification of polymorphic phases should be a mandatory test for Carvedilol in an official compendium. Acknowledgments: We thank FAPEMIG, FINEP, CAPES and CNPq for their financial support.
