Soliman S M, Abdel Malak N S, El-Gazayerly O N, Abdel Rehim A A
Department of Pharmaceutics, Faculty of Pharmacy, Cairo University, Egypt.
Drug Discov Ther. 2010 Dec;4(6):459-71.
The aim of this study was to develop suitable microemulsion gel systems for transdermal delivery that could assist dissolution enhancement of poorly water soluble celecoxib and thus improve its skin permeability. Long term oral administration of celecoxib causes serious gastrointestinal adverse effects, which makes it a good candidate for transdermal formulations, yet its low water solubility (4 mg/L) makes this challenging. Ternary phase diagrams were constructed using isopropyl myristate and oleic acid as oils, Tween 80 as surfactant, and Cremophor RH40 as cosurfactant. Microemulsion areas were identified and two systems each of 36 formulas were prepared and assessed for visual inspection, spreadability, pH measurements, and droplet size analysis. Drug release and in vitro permeation of celecoxib from microemulsion formulas through semi-permeable membranes and excised abdominal rabbit skin, respectively, were carried out and compared to celecoxib cream. In all tested formulas, celecoxib was released and permeation was at a higher rate than that from the corresponding cream. The optimized formula (F12) was found to be superior to all other formulas. This formula increased the permeation rate of celecoxib up to 11 times compared to that of the cream. Its stability was retained after one year of storage under ambient conditions and its anti-inflammatory effect was significantly higher than that of celecoxib cream and the oral commercial formula. Skin irritancy and histopathological investigation of rat skin revealed its safety. The results revealed that the developed microemulsion gel has great potential for transdermal delivery of celecoxib.
本研究的目的是开发适用于透皮给药的微乳凝胶系统，该系统可辅助提高难溶性塞来昔布的溶解度，从而改善其皮肤渗透性。长期口服塞来昔布会引起严重的胃肠道不良反应，这使其成为透皮制剂的理想候选药物，但其低水溶性（4 mg/L）给这一目标带来了挑战。使用肉豆蔻酸异丙酯和油酸作为油相、吐温80作为表面活性剂、聚氧乙烯蓖麻油RH40作为助表面活性剂构建三元相图。确定微乳区域，制备并评估了36种配方中的两种系统，进行外观检查、铺展性、pH测量和液滴大小分析。分别进行了塞来昔布从微乳配方通过半透膜和切除的兔腹部皮肤的药物释放和体外渗透实验，并与塞来昔布乳膏进行比较。在所有测试配方中，塞来昔布的释放和渗透速率均高于相应的乳膏。发现优化配方（F12）优于所有其他配方。与乳膏相比，该配方使塞来昔布的渗透速率提高了11倍。在环境条件下储存一年后，其稳定性得以保持，且其抗炎效果明显高于塞来昔布乳膏和口服市售配方。大鼠皮肤的皮肤刺激性和组织病理学研究表明其安全性良好。结果表明，所开发的微乳凝胶在塞来昔布透皮给药方面具有巨大潜力。
