Departmental of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, 125001, India.
Drug Delivery Research Laboratory, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India.
AAPS PharmSciTech. 2022 Mar 29;23(4):101. doi: 10.1208/s12249-022-02253-5.
The present piece of research work is framed for improving the solubility of ketoprofen by forming co-crystal using fumaric acid as a coformer. Co-crystal of ketoprofen and fumaric acid was prepared by simple solvent-assisted grinding method, containing drug and coformer as independent variables and solubility and % drug release were assumed to be dependent variables. Differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, nuclear magnetic resonance and scanning electron microscopy techniques were used to characterize the preparation of optimized batch of co-crystal and further, evaluated for in vitro and in vivo anti-inflammatory and analgesic activities. Based on results of solubility and dissolution rate studies the formulation showed magnified improvement in both the properties on co-crystallization. The values of Gibbs free energy are negative at all levels of carrier demonstrating spontaneity of the drug solubilization process. The IC value of optimized batch of co-crystal formulation and the pure drug was observed as 327.33 μg/ml and 556.11 μg/ml, respectively, demonstrating that co-crystal formulation possesses more percentage protection against protein denaturation than the drug ketoprofen. In vivo (anti-inflammatory and analgesic) activities revealed that optimized batch of co-crystal formulation delivered a rapid pharmacological response in Wistar rats and albino mice when compared with standard drug.
本研究工作旨在通过使用富马酸作为共晶形成剂形成共晶来提高酮洛芬的溶解度。采用简单的溶剂辅助研磨法制备了酮洛芬和富马酸共晶，药物和共晶形成剂分别作为自变量，溶解度和%药物释放作为因变量。采用差示扫描量热法、傅里叶变换红外光谱法、X 射线衍射法、核磁共振法和扫描电子显微镜技术对优化批次共晶的制备进行了表征，并进一步评价了其体外和体内抗炎和镇痛活性。基于溶解度和溶出速率研究的结果，该制剂在共结晶过程中显示出在这两种性质上的显著改善。在所有载体水平上，吉布斯自由能的值均为负，表明药物增溶过程是自发的。优化批次共晶制剂和原料药的 IC 值分别为 327.33μg/ml 和 556.11μg/ml，表明共晶制剂对蛋白质变性的保护率高于酮洛芬原料药。体内（抗炎和镇痛）活性研究表明，与标准药物相比，优化批次共晶制剂在 Wistar 大鼠和白化小鼠中表现出更快的药理反应。
