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热敏液体大豆卵磷脂/泊洛沙姆 407 基凝胶作为经皮给药载体的胶凝过程和药物释放特性研究。

Characterization of gelation process and drug release profile of thermosensitive liquid lecithin/poloxamer 407 based gels as carriers for percutaneous delivery of ibuprofen.

机构信息

Department of Pharmaceutical Technology and Cosmetology, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia.

Department of Pharmaceutical Technology and Cosmetology, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, P.O. Box 146, 11221 Belgrade, Serbia.

出版信息

Int J Pharm. 2015 Jul 25;490(1-2):180-9. doi: 10.1016/j.ijpharm.2015.05.040. Epub 2015 May 19.

Abstract

Suitability of liquid lecithin (i.e., solution of lecithin in soy bean oil with ∼ 60% w/w of phospholipids) for formation of gels, upon addition of water solution of poloxamer 407, was investigated, and formulated systems were evaluated as carriers for percutaneous delivery of ibuprofen. Formulation study of pseudo-ternary system liquid lecithin/poloxamer 407/water at constant liquid lecithin/poloxamer 407 mass ratio (2.0) revealed that minimum concentrations of liquid lecithin and poloxamer 407 required for formation of gel like systems were 15.75% w/w and 13.13% w/w, respectively, while the maximum content of water was 60.62% w/w. The systems comprising water concentrations in a range from 55 to 60.62% w/w were soft semisolids suitable for topical application, and they were selected for physicochemical and biopharmaceutical evaluation. Analysis of conductivity results and light microscopy examination revealed that investigated systems were water dilutable dispersions of spherical oligolamellar associates of phospholipids and triglyceride molecules in the copolymer water solution. Rheological behavior evaluation results indicated that the investigated gels were thermosensitive shear thinning systems. Ibuprofen (5% w/w) was incorporated by dispersing into the previously prepared carriers. Drug-loaded systems were physically stable at storage temperature from 5 ± 3°C to 40 ± 2°C, for 30 days. In vitro ibuprofen release was in accordance with the Higuchi model (rH>0.95) and sustained for 12h. The obtained results implicated that formulated LLPBGs, optimized regarding drug release and organoleptic properties, represent promising carriers for sustained percutaneous drug delivery of poorly soluble drugs.

摘要

液体卵磷脂(即大豆油中含有约 60%重量/重量磷脂的卵磷脂溶液)与聚氧乙烯 407 的水溶液混合后形成凝胶的适用性进行了研究,并将配方体系评估为布洛芬经皮给药的载体。在恒定的液体卵磷脂/泊洛沙姆 407 质量比(2.0)下,对伪三元体系液体卵磷脂/泊洛沙姆 407/水的配方研究表明,形成凝胶样体系所需的液体卵磷脂和泊洛沙姆 407 的最小浓度分别为 15.75%w/w和 13.13%w/w,而水的最大含量为 60.62%w/w。水浓度范围为 55 至 60.62%w/w 的体系为适合局部应用的软半固体,选择它们进行物理化学和生物药剂学评估。对电导率分析结果和光学显微镜检查的分析表明,所研究的体系是在共聚物水溶液中磷脂和甘油三酯分子的球形寡层聚集体的可水稀释分散体。流变行为评估结果表明,所研究的凝胶是热敏感的剪切稀化体系。将布洛芬(5%w/w)分散到先前制备的载体中。在 5±3°C至 40±2°C的储存温度下,载药系统在 30 天内物理稳定。体外布洛芬释放符合 Higuchi 模型(rH>0.95),持续 12h。所得结果表明,优化了药物释放和感官特性的 LLPBG 是用于难溶性药物持续经皮给药的有前途的载体。

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