Preparation and Solid-State Characterization of Ketoprofen-Succinic Acid-Saccharin Co-Crystal With Improved Solubility

Abstract

Objective: This study aimed to improve the solubility of Ketoprofen, a non-steroidal anti-inflammatory drug (NSAID) that belongs to the Biopharmaceutical Classification System (BCS) Class II, through co-crystallization using succinic acid and saccharin coformers in a 1:1:1 and 2:1:1 molar ratio. Methods: The slurry method was utilized to prepare the ketoprofen co-crystals, which were then subjected to various physical-chemical characterization techniques such as melting point determination, dissolution studies, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) spectroscopy. Results: The results showed that the 1:1:1 molar ratio of ketoprofen-succinic acid-saccharin co-crystal (Formula 1) exhibited higher solubility than the solubility standard of Ketoprofen and the 2:1:1 molar ratio of the co-crystal (Formula 2). The dissolution profile (Q30) of Formula 1, Formula 2, and standard Ketoprofen were 96.73±1.77, 93.09±1.16, and 70.22±4.72, respectively. These findings suggest that co-crystallization with succinic acid and saccharin conformers using the slurry method can significantly enhance the solubility of Ketoprofen. Conclusion: The 1:1:1 molar ratio of ketoprofen-succinic acid-saccharin co-crystal (Formula 1) was the most effective formulation among the tested samples, demonstrating the highest solubility. This research may provide valuable insights for developing novel drug formulations with improved bioavailability and therapeutic efficacy.

Quantitative Determination of Some Non-Steroidal Anti-Inflammatory Drugsand Their Acid Dissociation Constants by Direct Potentiometry

“…For this reason, the manufacture and use of drugs require reliable methods of quality control of bulk substances and pharmaceutical formulations. Various methods such as titrimetry, spectrophotometry, and spectrofluorimetry have been reported for the determination of these drugs [12][13][14][15]. Analysis based on capillary zone electrophoresis, HPLC, and GC-MS methods [16][17][18][19][20] are also available.…”