Abstract

Curcumin is known for its various therapeutic properties like anti-inflammatory, antioxidant, anticancer, however, its oral use is restricted due to its low solubility and dissolution rate in alkaline pH. In this study co-amorphous mixture of curcumin–ascorbic acid (CU:AA) of different molar ratios was prepared using the ball milling method. The solubility and characterization of the mixture were studied using FTIR, DSC, and XRD study. Mixture (1:0.50) molar ratio showed the highest solubility and was formulated in pellets dosage and optimized using 3² full factorial designs. The solubility results revealed that a significant increase (p < 0.005) in the solubility of curcumin by the ratio 1:0.50 (212 ± 12 µg/ml) compared to the pure drug (90.0 ± 10 µg/ml). XRD and DSC studies confirmed the formation of amorphous curcumin, whereas FTIR elucidated weak hydrogen interactions. In-vitro dissolution study results showed the (CU:AA) ratio (1:0.50) higher percent drug release (81.61 ± 5.12%) compared to the pure drug (19.44 ± 4.60%). The developed formulations are found to be stable. Therefore, the prepared pellets of co-amorphous mixture enhance the solubility, dissolution rate, and stability of curcumin in higher pH, which will become a promising approach for combination therapy in the treatment of ulcerative colitis patients.

摘要

姜黄素以其多种治疗特性而闻名，例如抗炎，抗氧化剂，抗癌，但是由于其在碱性pH值下的低溶解度和溶解速度，其口服用途受到限制。在这项研究中，使用球磨法制备了不同摩尔比的姜黄素-抗坏血酸（CU：AA）共非晶混合物。使用FTIR，DSC和XRD研究了混合物的溶解度和特性。混合物（1：0.50）的摩尔比显示出最高的溶解度，并以小球剂量配制，并使用3 ²全因子设计进行了优化。溶解度结果表明，显着增加（p 与纯药物（90.0±10 µg / ml）相比，姜黄素的溶解度为<1：0.50（212±12 µg / ml）<0.005）。XRD和DSC研究证实了无定形姜黄素的形成，而FTIR阐明了弱的氢相互作用。体外溶出度研究结果显示，与纯药物（19.44±4.60％）相比，（CU：AA）比（1：0.50）的药物释放百分比更高（81.61±5.12％）。发现开发的制剂是稳定的。因此，制备的无定形混合物小丸可提高姜黄素在较高pH下的溶解度，溶解速率和稳定性，这将成为溃疡性结肠炎患者联合治疗的有希望的方法。