PRODUCTION, CHARACTERISATION AND PHARMACEUTIC PERFORMANCE EVALUATION OF CIPROFLOXACIN HYDROCHLORIDE-SALICYLIC ACID MULTICOMPONENT CRYSTAL

• Main Author: Oktaviary, Rozana
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/45777
• Institution: Institut Teknologi Bandung

Ciprofloxacin is a member of fluorquinolone antibiotics which is classified into biopharmaceutics classification system (BCS) class IV. In present days, ciprofloxacin is marketed as HCl salt due to its solubility. Cocrystal manufacturing is another approach in the engineering of active pharmaceutical ingredients to improve biopharmaceutical performance. In this study, a cocrystal of ciprofloxacin HCl with salicylic acid was prepared to obtain a product with superior solubility and dissolution profile. Ciprofloxacin HCl and salicylic acid with an equimolar ratio of 1:1 were dissolved in a combination of methanol-water and ethanol-water solvents. The resulting product was characterized using Fourier-transform infrared spectroscopy (FTIR), thermal analysis with electro thermal as well as differential thermal analysis (DTA)/thermogravimetry (TG) and diffractometry with powder X-ray diffractometry (PXRD). Optimization of manufacturing methods and duration of sonication was carried out to determine the most efficient cocrystal production process. The solubility and dissolution tests were carried out to compare the performance of cocrystal to ciprofloxacin HCl. Ciprofloxacin HCl-salicylic acid cocrystal was successfully obtained from solvent evaporation method using methanol-water (1:1), assisted by sonication for 20 minutes. Characterization with FTIR revealed distinctive peaks at 1697, 1616, 1546 and 3425 cm -1 representing intermolecular hydrogen bonds formation. Thermal analysis showed endothermic peaks at 123.5°C; 174.6°C and 221.7°C which represent water evaporation, melting point and decomposition. Diffractogram revealed several peaks with high intensity at diffraction angle values of 6.16°; 14.48°; 20.06°; 22.35° and 28.07°. Characterization results suggested that the multicomponent system obtained was a hydrate cocrystal that had never been discovered before. The solubility and dissolution test were evaluated using validated method with derivatized UV-Visible absorption spectrum. Cocrystal increased the solubility of ciprofloxacin HCl 1.3 folds in pH 1.2 as well as water and 1.1 folds in pH 6.8. During dissolution test, cocrystal reached a steady state with dissolution percentage over 80%, 90 minutes earlier compared to ciprofloxacin HCl alone.