Vol. 7, Issue 1, Part E (2025)

Introduction: It is exceedingly challenging to achieve adequate bioavailability and therapeutic efficacy with drugs that are poorly soluble in water. As an alternative to polymer-based amorphous solid dispersions, co-amorphous drug-drug systems have gained popularity due to their increased solubility, possibility of fixed-dose combination therapy, and better stability. In order to enhance the drug solubility and prolonged release of the combination therapy, this research aims to investigate the viability of a co-amorphous system combining celecoxib (CEL) with naproxen (NAP). Materials and Methods: Solvent evaporation was employed to fabricate CEL and NAP co-amorphous systems in 1:1 and 1:2 molar ratios, respectively. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), saturation solubility investigations, and in vitro dissolution tests were utilized to examine the formulations. The individuals' physical stability was assessed following three months at 40 °C and 75% relative humidity. Dissolution tests were done in 900 mL of phosphate buffer with a pH of 6.8 using a USP type II device at 37±0.5 °C. Results: Co-amorphous systems exhibited a singular glass transition temperature (Tg) at 68.4 °C, indicating effective co-amorphization, as demonstrated by DSC analysis, which showed the disappearance of the melting endotherms of CEL (161 °C) and NAP (153 °C). PXRD showed complete amorphization because there were no unique crystalline peaks. FTIR suggested that hydrogen bonding between the CEL sulfonamide and NAP carboxyl groups could be a way that intermolecular salts are formed. The 1:1 co-amorphous system raised the saturation solubility of CEL from 7.2±0.6 µg/mL (the pure medication) to 64.5±2.1 µg/mL, which is almost nine times higher. Conversely, the solubility of NAP increased from 15.8±1.2 µg/mL to 53.6±1.9 µg/mL. After 60 minutes of in vitro dissolution, the cumulative release was 82.3% for CEL and 78.6% for NAP. This was 18.4% and 26.9% higher than what pure medications would have released. According to the stability studies, there was no recrystallization after three months, and the Tg and dissolution profiles stayed the same. Conclusion: The celecoxib-naproxen co-amorphous system made combination therapy possible without polymeric excipients. This system greatly increased solubility, dissolving rate, and physical stability. This dual-drug co-amorphous technique is an interesting way to improve the oral distribution of drugs that don't dissolve well in sustained-release formulations.