Tu Jiasheng, Pang Hui, Yan Zhen, Li Pengmei
Department of Pharmaceutics, China Pharmaceutical University, Nanjing, P. R. China.
Drug Dev Ind Pharm. 2007 Oct;33(10):1142-50. doi: 10.1080/03639040701397381.
Methoxy poly(ethylene glycol)-poly(D, L-lactide) block copolymer was tested as an ocular permeation enhancer for pirenzepine hydrochloride. The block copolymers with the methoxy poly(ethylene glycol) to poly(D, L-lactide) weight ratio of 80/20, 50/50, 40/60 were synthesized by a ring-opening polymerization procedure. In vitro transcorneal experiments demonstrated that the block copolymer 80/20 significantly enhanced the transcorneal permeation of pirenzepine at the mass ratio of 1/1.4 (pirenzepine hydrochloride/copolymer). Interaction between pirenzepine and copolymer was identified by infrared spectroscopy analysis and dialysis experiments. Ocular pharmacokinetics of pirenzepine/copolymer preparation by in vivo instillation experiments confirmed that block copolymer could enhance the ocular penetration of pirenzepine. Ocular chronic toxicity experiments of block copolymer and pirenzepine/copolymer preparation were studied on rabbits, and no significant toxicity in both groups was observed within 9 months. It could conclude that pirenzepine/copolymer preparation is effective and safe in ocular delivery of pirenzepine.
甲氧基聚（乙二醇）-聚（D，L-丙交酯）嵌段共聚物被作为盐酸哌仑西平的眼部渗透促进剂进行了测试。通过开环聚合法合成了甲氧基聚（乙二醇）与聚（D，L-丙交酯）重量比为80/20、50/50、40/60的嵌段共聚物。体外透角膜实验表明，在质量比为1/1.4（盐酸哌仑西平/共聚物）时，80/20的嵌段共聚物显著增强了哌仑西平的透角膜渗透。通过红外光谱分析和透析实验确定了哌仑西平与共聚物之间的相互作用。通过体内滴注实验对哌仑西平/共聚物制剂的眼部药代动力学进行了研究，证实嵌段共聚物可增强哌仑西平的眼部渗透。对兔子进行了嵌段共聚物和哌仑西平/共聚物制剂的眼部慢性毒性实验，在9个月内两组均未观察到明显毒性。可以得出结论，哌仑西平/共聚物制剂在眼部递送哌仑西平时是有效且安全的。
