Kassem A A, Marzouk M A, Ammar A A, Elosaily G H
Department of Pharmaceutics, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo, Egypt.
Drug Discov Ther. 2010 Oct;4(5):373-9.
This study sought to formulate and evaluate a self-nanoemulsified drug delivery system (SNEDDS) for clotrimazole (CT), a poorly water-soluble antimycotic drug, used in vaginal delivery. SNEDDS was developed to increase the CT dissolution rate, solubility, and ultimately bioavailability. The solubility of CT in various oils, surfactants, and co-surfactants was determined. Based on solubility studies, oil phase (oleic acid without or with coconut oil), surfactant (Tween 20), and co-surfactants (PEG 200 and n-butanol) were selected and grouped in two combinations for phase studies. Pseudo-ternary phase diagrams were used to evaluate the area of self-nanoemulsification. Essential properties of the prepared systems with regard to emulsion droplet size and turbidity value were determined. In order to investigate the potential for interaction between any of the SNEDDS ingredients used, FTIR spectroscopy was performed. In vitro release studies were performed with SNEDDS formulations in capsules, and the plain drug served as a control. The droplet size of the nanoemulsion was greatly affected by the ratio of the surfactant and co-surfactant. Based on the results with regard to droplet size, turbidity values, and complete drug release after 3 h, three optimized formulations were selected; each contained oleic acid/coconut oil/Tween 20/PEG 200/n-butanol in ratios of 10:0:60:15:15 (%, w/w), 7.5:2.5:53.5:13.3:13.3 (%, w/w), and 6.7:3.3:60:10:10 (%, w/w), respectively. Results suggested that the prepared SNEDDS formulations produced acceptable properties in terms of immediate drug release and could increase the bioavailability of CT.
本研究旨在制备并评估用于克霉唑（CT）的自纳米乳化药物递送系统（SNEDDS），CT是一种水溶性差的抗真菌药物，用于阴道给药。开发SNEDDS是为了提高CT的溶解速率、溶解度，并最终提高其生物利用度。测定了CT在各种油、表面活性剂和助表面活性剂中的溶解度。基于溶解度研究，选择油相（不含或含椰子油的油酸）、表面活性剂（吐温20）和助表面活性剂（聚乙二醇200和正丁醇），并将其分为两种组合进行相研究。使用伪三元相图评估自纳米乳化区域。测定了所制备体系在乳液滴径和浊度值方面的基本性质。为了研究所用任何SNEDDS成分之间相互作用的可能性，进行了傅里叶变换红外光谱（FTIR）分析。用胶囊中的SNEDDS制剂进行体外释放研究，以原料药作为对照。纳米乳液的滴径受表面活性剂和助表面活性剂比例的影响很大。基于滴径、浊度值和3小时后药物完全释放的结果，选择了三种优化制剂；每种制剂分别含有比例为10:0:60:15:15（%，w/w）、7.5:2.5:53.5:13.3:13.3（%，w/w）和6.7:3.3:60:10:10（%，w/w）的油酸/椰子油/吐温20/聚乙二醇200/正丁醇。结果表明，所制备的SNEDDS制剂在药物速释方面具有可接受的性质，并且可以提高CT的生物利用度。
