用共溶度法提高青蒿素和姜黄素在静脉给药系统中的溶解度

V. Thakkar, R. Dhankecha, M. Gohel, P. Shah, T. Pandya, T. Gandhi
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引用次数: 4

摘要

本研究旨在采用共溶性方法提高难溶性抗疟药物青蒿素和姜黄素的溶解度,并开发非肠外注射水溶液。两种药物的溶解度增强是通过共溶性方法实现的。采用以苯甲醇、peg400和吐温80为表面活性剂的三元共溶剂体系制备了肠外注射剂。青蒿素和姜黄素在苯甲醇和peg400中的溶解度较高。由苯甲醇、peg400和吐温80组成的共溶剂体系,其体积分数分别为0.3、0.9和0.2,表明青蒿素(90 mg / ml)和姜黄素(180 mg / ml)的最小溶解度要求。对该制剂的pH值、清晰度、粘度、渗透压和无菌性进行了表征,所述参数在可接受范围内。体外红细胞毒性研究表明,优化后的配方静脉给药是安全的。体外抗疟试验表明,青蒿素姜黄素肠外制剂的抗疟效果优于奎宁和蒿甲醚与甲苯胺联合用药。稳定性研究表明,优化后的批料的理化特性没有变化。研究表明,青蒿素和姜黄素可通过共偿付方法配制成有效治疗疟疾感染的肠外注射制剂
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Enhancement of Solubility of Artemisinin and Curcumin by Co-Solvency Approach for Application in Parenteral Drug Delivery System
The aim of present study was to enhance solubility of poorly soluble antimalarial drugs, Artemisinin and Curcumin by adopting  Co-solvency approach and to develop parenteral aqueous injectable solution. Solubility enhancement of both drugs was achieved using co-solvency approach. The parenteral injection was prepared by using a ternary co-solvent system which comprised of benzyl alcohol, PEG 400 and tween 80 (as surfactant). Solubility of Artemisinin and Curcumin was found to be higher in benzyl alcohol and PEG 400. Co-solvent system comprising of  benzyl alcohol, PEG 400 and tween 80 in volume fraction of 0.3, 0.9 and 0.2 respectively showed the minimum required solubility of Artemisinin (90 mg per ml) and Curcumin (180 mg per ml). The parenteral injectable formulation was characterized for pH, clarity, viscosity, osmolarity and sterility and the stated parameters were found in acceptable range.  In-vitro erythrocyte toxicity study showed that intravenous administration of optimized formulation will be safe. In-vitro antimalarial assay indicated that efficacy of artemisinin and curcumin parenteral formulation was greater than quinine and combination of Artemether and Lumefantrine. Stability study of the optimized batch showed no change in physical and chemical characteristics. Based on study, one can conclude that Artemisinin and Curcumin can be successfully formulated as parenteral injectable formulation by co-solvency approach for the effective treatment of malarial infection
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