目的 制备氯替泼诺眼用微乳,以提高药物的治疗效果。方法 以溶解度、乳化能力和伪三元相图法筛选油相、乳化剂和助乳化剂种类及其含量,对所制备微乳的理化性质,微观结构,体外释放能力和角膜渗透能力进行考察,并初步评价眼部药效学。结果 经筛选得到氯替泼诺眼用微乳的最佳处方;其粒径、多分散系数(PDI)等理化性质良好;体外释放结果显示微乳比混悬滴眼液释放更快且更加完全;微乳的角膜渗透量比混悬滴眼液多,且渗透速率更快;药效学研究显示,在减少给药次数和降低给药浓度的情况下,氯替泼诺眼用微乳治愈炎症的时间仍然比混悬滴眼液短,表明氯替泼诺微乳提高了药物的疗效。结论 制备的氯替泼诺眼用微乳具有工艺简单、起效快、释药持久的特点,能够提高药物的疗效,适合眼部给药。
Abstract
OBJECTIVE To prepare loteprednol etabonate (LE) ophthalmic microemulsion and improve the efficacy. METHODS The optimum oil phase, emulsifier and coemulsifier and their contents were selected by solubility, emulsifying ability and pseudo ternary phase diagram. Its physical and chemical properties, microstructure, in vitro release ability and corneal permeability were investigated, and the ocular pharmacodynamics was preliminarily evaluated. RESULTS The best formulation of LE ophthalmic microemulsion was obtained. Its particle size, PDI and other physical and chemical properties were good. The in vitro release results showed that LE microemulsion released faster and more completely than suspension eye drops. The corneal penetration of microemulsion was more than that of suspension eye drops, and the penetration rate was faster.Pharmacodynamic studies showed that the cure time of LE ophthalmic microemulsion was shorter than that of suspension eye drops, indicating that LE microemulsion improved the efficacy. CONCLUSION The prepared LE ophthalmic microemulsion has the characteristics of simple process, fast onset and long-lasting release, which can improve the efficacy of the drug and is suitable for ocular administration.
关键词
氯替泼诺 /
微乳 /
伪三元相图 /
体外释放 /
角膜渗透
{{custom_keyword}} /
Key words
loteprednol etabonate /
microemulsion /
pseudo-ternary phase diagram /
in vitro release /
corneal penetration
{{custom_keyword}} /
中图分类号：
R944
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] CHEN A J, HAN Z S, HUANG X Y. Improved synthesis of loteprednol etabonate[J]. Chin J Med Chem(中国药物化学杂志), 2003,14(5): 58-59.
[2] TANG H, JIN X, YAN X N. Pharmacokinetics of loteprednol etabonate in beagle dogs through different routes of administration[J]. Chin Pediatr Integr Tradit West Med(中国中西医结合儿科学) 2018, 10(3): 185-188,277.
[3] JANG W. Handbook of Ophthalmic Clinical Drugs (眼科临床药物手册)[M]. Nanjing:Phoenix Science Press, 2008. 5.
[4] TALEGAONKAR S, AZEEM A, AHMAD F J, et al. Microemulsions: a novel approach to enhanced drug delivery[J]. Recent Pat Drug Deliv Formul, 2008, 2(3): 238-257.
[5] ZHU T, KANG W, YANG H, et al. Advances of microemulsion and its applications for improved oil recovery[J]. Adv Colloid Interface Sci, 2022, 299(10):25-27.
[6] NIRAV P, HAPPY N, MIHIR R, et al. Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability[J]. Drug Deliv, 2016, 23(9):3712-3723.
[7] GAO Y,ZHANG Y, FU H J, et al. Preparation of tacrolimus ophthalmic microemulsion and investigation of the method for determination of loaded drugs[J]. J Int Pharm Res(国际药学研究杂志), 2017, 44(5): 453-460.
[8] PAN G L, JIA X B, WEI H H, et al. Comparison among several preparation methods for pseudo-ternary phase diagrams of pharmaceutical microemulsions?[J].J China Pharm(中国药房), 2006,17(1): 21-23.
[9] LIU J, YANG Y N, HE J, et al. Optimization of Preparation of Alprostadil Microemulsions[J]. Chin J Pharm(中国医药工业杂志), 2015, 46(6): 586-591.
[10] MIGUEL M D G, BURROWS H D, PEREIRA M A E, et al. Probing solute distribution and acid-base behaviour in water-in-oil microemulsions by fluorescence techniques[J]. Colloids Surfaces A:Physicochem Eng Aspec, 2001, 176(1): 85-99.
[11] GAAFARPASSENTM E, ABDALLAH OSSAMA Y, FARID RAGWA M,et al. Preparation, characterization and evaluation of novel elastic nano-sized niosomes (ethoniosomes) for ocular delivery of prednisolone[J]. J Lipos Res, 2014, 24(3):204-215.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
PDF(1963 KB)
