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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
Finasteride is a specific competitive inhibitor of steroid type-II 5α-reductase, an intracellular enzyme that converts testosterone to dihydrotestosterone (DHT) and is widely used for the treatment of benign prostatic hyperplasia (BPH), prostate cancer , and androgenetic alopecia. Polymorphs are known to give rise to significant differences in the physicochemical properties of the compound as melting point, density, morphology, solubility and colour. Thus, proper monitoring of solid-state forms, both qualitative and quantitative, is crucial in order to ensure high-quality products. The crystal structures of finasteride appear in the Cambridge Crystal Structure Database (CSD) under the codes WOLXOK01 and WOLXOK02 for Form I and WOLXOK03 for Form II. In this context, the aim of this work was study the behavior of the chemical structure and physicochemical properties of polymorphic forms, and to evaluate the possible influence in the dissolution profile and stability of capsules. A stability study was carried out at 500C for 3 months. The Form II of finasteride was obtained by heating Form I to 2350C for 30 minutes. The techniques X-ray diffraction, infrared spectroscopy and thermal analysis were applied to characterize the Forms. The solubility of finasteride polymorphs was determined by equilibrium solubility method. For the dissolution test, water was used as dissolution medium and the basket apparatus at 100 rpm. The samples were analyzed by HPLC at 210 nm. Differences in X-ray diffraction and infrared spectra of the two polymorphs were observed. The DSC curves showed Form I melting peak at 2570C and solid-solid transformation to Form II at about 2300C. In the solubility study was observed higher Form II solubility than Form I in most evaluated pHs. The interaction of the Forms I and II with capsule excipients may have been different since the dissolution profile of the capsules showed higher release to the Form I. In the stability study, the finasteride content was stable for two Forms, however, the dissolution profile of Form II showed greater decline than the Form I. In conclusion, the results show that the dissolution profiles polymorphism may influence the quality of finasteride capsules, being necessary there be a polymorphic quality control for this dosage Form. Acknowledgments: PNPD CAPES and FAPEMIG
