Fernández-Carballido A, Herrero-Vanrell R, Molina-Martínez I T, Pastoriza P
Departamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Avda. Complutense s/n, Universidad Complutense, 28040 Madrid, Spain.
Int J Pharm. 2004 Jul 26;279(1-2):33-41. doi: 10.1016/j.ijpharm.2004.04.003.
The objective of this study was the development and optimisation of biodegradable PLGA microspheres loaded with ibuprofen destined for intraarticular administration. The formulation was designed to provide "in vitro" therapeutic concentrations of ibuprofen (8 microg/ml) for as long as possible. The solvent evaporation method based on an o/w emulsion was used to form the microparticles. The polymer used was Poly (D,L-lactide-co-glicolide) 50:50 (PLGA), of different molecular weights (Mw) (34,000, 48,000 and 80,000 Da). In order to get a more controlled release rate of ibuprofen, a biodegradable oil, Labrafil M1944CS, polyethylene glycol 300 derivative, was used as an additive. The formulation was optimised by means of an experimental design, 2(3) being the variables: X(1) = PLGA Mw; X(2) = initial ibuprofen:polymer ratio; X(3) = percentage of Labrafil. The theoretical profile yielding in vitro "therapeutic" concentrations of ibuprofen (8 microg/ml) was calculated. The experimental profiles obtained for the formulations tested were compared with the theoretical one by means of the difference factor (f(1)). In all cases, the addition of Labrafil lowered the initial ibuprofen burst, prolonging the release rate of the drug from 24 h (without additive) up to 8 days incorporating the oil. The microspheres made from the PLGA (Mw = 34,000 Da) with Labrafil addition (10%) and ibuprofen:polymer (15%) ratio (formulation 1) yielded the most suitable release profiles. Forty milligram of the selected formulation (formulation 1), was sufficient to provide in vitro "therapeutic" concentrations of ibuprofen (8 microg/ml) up to 8 days. Labrafil modulates the release rate of donor-acceptor substances such as ibuprofen.
本研究的目的是开发并优化用于关节腔内给药的载有布洛芬的可生物降解聚乳酸-羟基乙酸共聚物（PLGA）微球。该制剂旨在尽可能长时间地提供布洛芬的“体外”治疗浓度（8微克/毫升）。基于水包油乳液的溶剂蒸发法用于形成微粒。所用聚合物为不同分子量（Mw）（34000、48000和80000道尔顿）的聚（D，L-丙交酯-乙交酯）50:50（PLGA）。为了获得更可控的布洛芬释放速率，使用了一种可生物降解的油Labrafil M1944CS（聚乙二醇300衍生物）作为添加剂。通过实验设计对制剂进行优化，变量为2(3)：X(1)=PLGA Mw；X(2)=初始布洛芬与聚合物的比例；X(3)=Labrafil的百分比。计算了产生布洛芬“治疗”浓度（8微克/毫升）的理论曲线。通过差异因子（f(1)）将测试制剂获得的实验曲线与理论曲线进行比较。在所有情况下，添加Labrafil均降低了布洛芬的初始突释，使药物释放速率从24小时（无添加剂）延长至加入该油后的8天。添加了10%Labrafil且布洛芬与聚合物比例为15%（制剂1）的由PLGA（Mw = 34000道尔顿）制成的微球产生了最合适的释放曲线。40毫克选定的制剂（制剂1）足以在长达8天的时间内提供布洛芬的“体外”治疗浓度（8微克/毫升）。Labrafil可调节诸如布洛芬等供体-受体物质的释放速率。
