Jain Subheet Kumar, Puri Richa
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, Punjab, 143 005 India.
Curr Drug Deliv. 2014;11(3):401-14. doi: 10.2174/1567201810666131210112150.
5-Fluorouracil (5-FU) is one of the most effective antineoplastic agents used for the treatment of skin cancers and actinic keratosis (AK). Currently commercial formulation for topical 5-FU administration is available in the form of solution or cream. Commercial topical formulations are associated with the limitation of very short retention time at the administration site resulting in very poor skin permeation and deposition of drug. In the present study attempt was made for the preparation, optimization and characterization of bioadhesive gel formulations for localized delivery of 5-FU. Four bioadhesive gel formers, Carbopol 934, Carbopol 980, Methylcellulose (MC) and Poloxamer 188 were selected for the preparation of 5-FU bioadhesive gel formulations. The formulations were characterized for characteristic parameters including bioadhesive strength, skin deposition and interaction study. Carbopol 934 based bioadhesive gel formulation at the concentration of 1.5% w/w showed the best physicochemical properties such as viscosity (2670±12.2 cP), which was similar to the value obtained with the marketed cream (2870±14.4 cP), highest skin deposition (1290±56.4μg) and bioadhesive strength (18.62 gf). Cutaneous irritation of optimized bioadhesive gel formulations was also tested using the Draize test and only very slight erythema and no oedema was observed. In comparison, marketed formulation showed well defined erythema along with oedema formation. The result of the present study demonstrated that formulation of Carbopol 934 based 5-FU bioadhesive gel is a better alternative to the traditional cream base for enhanced topical delivery of 5-FU. The developed formulation will have the ease of application, better skin deposition and sustained release characteristic with reduced skin toxicity.
5-氟尿嘧啶（5-FU）是用于治疗皮肤癌和光化性角化病（AK）的最有效抗肿瘤药物之一。目前，用于局部给药5-FU的商业制剂有溶液或乳膏形式。商业局部制剂的局限性在于药物在给药部位的保留时间非常短，导致皮肤渗透和药物沉积很差。在本研究中，尝试制备、优化和表征用于5-FU局部递送的生物粘附凝胶制剂。选择了四种生物粘附凝胶形成剂，即卡波姆934、卡波姆980、甲基纤维素（MC）和泊洛沙姆188来制备5-FU生物粘附凝胶制剂。对制剂的特征参数进行了表征，包括生物粘附强度、皮肤沉积和相互作用研究。浓度为1.5%w/w的基于卡波姆934的生物粘附凝胶制剂表现出最佳的物理化学性质，如粘度（2670±12.2 cP），与市售乳膏（2870±14.4 cP）的值相似，皮肤沉积最高（1290±56.4μg）和生物粘附强度（18.62 gf）。还使用Draize试验测试了优化后的生物粘附凝胶制剂的皮肤刺激性，仅观察到非常轻微的红斑，没有水肿。相比之下，市售制剂表现出明确的红斑以及水肿形成。本研究结果表明，基于卡波姆934的5-FU生物粘附凝胶制剂是传统乳膏基质的更好替代品，可增强5-FU的局部递送。所开发的制剂将具有易于应用、更好的皮肤沉积和持续释放特性以及降低的皮肤毒性。
