Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Drug Deliv. 2011 Jan;18(1):38-45. doi: 10.3109/10717544.2010.509364. Epub 2010 Aug 31.
For the treatment of ocular keratitis acyclovir, as a highly specific inhibitor of herpes virus replication, is applied topically into the eye. The objective of this study was to design and evaluate freeze-dried, bioadhesive and biodegredable acyclovir ocular minitablets for prolonged local drug action. The sponge-like nature of the lyophilized ocular minitablets ensures rapid hydration and gelation of these tablets in the eye and thus would reduce the foreign body sensation. The polymers used were sodium carboxymethylcellulose (NaCMC), hydroxypropylmethylcellulose (HPMC), xanthan gum, chitosan and Carbopol 943P. The minitablets were evaluated for drug content, weight variation, bioadhesion, water uptake and in vitro drug release. In addition, the rheological characteristics of the polymers solutions were investigated. Rheological data revealed that all tested polymers exhibited pseudoplastic behaviour which is required to minimize interference with blinking. Drug release was found to be affected by the type and concentration of polymer. The order of sustainment was chitosan > xanthan > HPMC > Carbopol > NaCMC. Water uptake study, dissolution rate of the polymers and viscosity measurements could explain the different release profiles of the drug from the polymers. Chitosan minitablet was chosen for its significant sustained release and good bioadhesive property for in vivo study in rabbits. The tablet showed a good permeation into the cornea in comparison to the commercially available Zovirax(®) eye ointment. In conclusion, chitosan ocular minitablets containing acyclovir could be considered as a promising sustained drug delivery system for ocular keratitis treatment.
对于眼部角膜炎的治疗，阿昔洛韦作为一种高度特异性的疱疹病毒复制抑制剂，被局部应用于眼部。本研究旨在设计和评估可冻干、生物黏附性和可生物降解的阿昔洛韦眼部微型片剂，以延长局部药物作用。冻干眼部微型片剂的海绵状性质确保了这些片剂在眼部的快速水合和凝胶化，从而减少异物感。所用的聚合物为羧甲基纤维素钠（NaCMC）、羟丙基甲基纤维素（HPMC）、黄原胶、壳聚糖和卡波姆 943P。微型片剂的药物含量、重量变化、生物黏附性、吸水量和体外药物释放进行了评估。此外，还研究了聚合物溶液的流变特性。流变数据表明，所有测试的聚合物都表现出假塑性行为，这是最小化眨眼干扰所必需的。药物释放受聚合物的类型和浓度的影响。维持时间的顺序为壳聚糖＞黄原胶＞HPMC＞卡波姆＞NaCMC。吸水量研究、聚合物的溶解速率和粘度测量可以解释药物从聚合物中不同的释放曲线。壳聚糖微型片剂因其显著的缓释和良好的生物黏附性而被选择用于兔体内研究。与市售的 Zovirax（®）眼膏相比，该片剂显示出良好的穿透角膜能力。总之，含有阿昔洛韦的壳聚糖眼部微型片剂可被认为是治疗眼部角膜炎的一种有前途的缓释药物传递系统。
