曲安奈德巩膜植入剂的制备及体外释放特性考察.docVIP

曲安奈德巩膜植入剂的制备及体外释放特性考察 胡 蕾，刘松青，代 青 （第三军医大学西南医院药学部，重庆 400038） 提要：目的 制备醋酸曲安奈德（TAA）-聚乳酸（PLA）植入剂（Implant），考察醋酸曲安奈德植入剂的体外释药特性。方法 采用熔融-挤出法制备TAA-PLA 植入剂，高效液相色谱法测定TAA含量，绘制体外释放曲线。结果 制得的植入剂为直径0.8㎜，长约8㎜，重约8mg的白色柱状物，其中TAA的载药量为30%，体外释放速率平稳且缓慢，第30天时TAA的累积释放率为75.84%，药物体外释放符合Higuchi方程 Q = 0.137×(t - 0.752)1/2。结论 所制备的TAA-PLA 植入剂对药物TAA有明显的缓释效果，且在体内可生物降解，毒副作用小，有望成为TAA的眼部新型给药制剂。 关键词：聚乳酸；醋酸曲安奈德；眼色素层炎；巩膜植入剂 Preparation and release study of triamcinolone acetonide acetate scleral implant in vitro Abstract: Objective To prepare triamcinolone-acetonide-acetate (TAA)-polylactic acid(PLA) Implant and investigate its drug release in vitro. Methods The TAA-PLA Implant was prepared by melt-extrude technique. The drug release of TAA in vitro was determined by efficiency liquid chromatography (HPLC). Results The implant was white pillar with 8 mm in length, 8 mg in weight, and 0.8 mm in diameter. The drug loading was 30%. The drug release was at a steady and slow rate. Its accumulation release rate is 75.84% on the 30th day. Drug release profile in vitro was in accordance with Higuchi equation Q = 0.137×(t - 0.752)1/2. Conclusion These results, indicating that the studied TAA-PLA Implant system had the evident effect in delaying the release of TAA and could be biological degradation in vivo with little side effect, might be a novel vehicle for the topical use of TAA. Key words: PLA; Triamcinolone Acetonide Acetate; Uveitis; Scleral implant 眼植入剂[1]（Eye Implant）是一种长效定量缓释的新型药物制剂，可在眼内长期保持药物的有效治疗浓度，克服药物全身毒性大和玻璃体内半衰期短的缺点，适用于需要长期治疗的某些眼科疾患，分为非蚀解型和蚀解型两类[2]。Alza公司上市了一种乙烯-醋酸乙烯共聚物的载万古霉素植入剂来实现药物的控释，可以在下眼睑持续释放一周的高全身增量法或频繁的眼球内注射来实现，但毒副作用较大[3]。本文以聚乳酸（PLA）为基质，醋酸曲安奈德( triamcinolone acetonide acetate ,TAA)为模型药物，采用熔融-挤出成型法制备巩膜植入剂，建立了用高效液相色谱（HPLC）测定植入剂中TAA含量的方法，并对其体外释放特性进行了考察，为TAA新剂型的研究提供依据。 仪器与试药 1.1 仪器 高效液相色谱系统（Waters Alliance2690）；HJ-6A型多头磁力加热搅拌器（常州国华电器有限公司）；Photodiode Array Detector (Waters 996)；3531型离心机（德国ABBOTT PARK 公司）；THZ-9213型台式恒温振荡器（上海跃进医疗器械厂）；PP-15E型PH计（SARTORIUS AG 公司）；DW-Ⅱ型调温电热器（江苏竹行校办无线电元件厂）；BP-211S