In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions
In vitro release of diclofenac diethylamine from caprylocaproyl macrogolglycerides based microemulsions
复制标题
DOI：
10.1016/j.ijpharm.2005.02.014
复制
发表时间：
2005-05-30
影响因子：
5.8
通讯作者：
Stupar, M
中科院分区：
文献类型：
--
作者：
Djordjevic, L;Primorac, M;Stupar, M
本研究的目的是确定处方参数和载体结构对两亲性药物双氯芬酸二乙胺（DDA）从含有PEG-8辛酸/癸酸甘油酯（表面活性剂）、聚甘油-6二油酸酯（助表面活性剂）、肉豆蔻酸异丙酯和水的微乳载体中体外释放速率的影响。从所建立的表面活性剂-助表面活性剂质量比的拟三元相图中，（K-m，1：1）、油-表面活性剂-助表面活性剂的最佳质量比值（O/SC 0.67-1.64）用于配制具有相似浓度的亲水性，亲脂两亲相表征实验结果表明，微乳液为双连续或非球形水-所选微乳液载体的连续内部结构。低的水/肉豆蔻酸异丙酯的表观分配系数DDA以及电导率和表观粘度值升高的研究微乳液制剂含有1.16%（w/w）的DDA，表明药物分子主要分配在水相中，最有可能自聚集和与界面膜相互作用。采用转桨溶出仪，考察了DDA在水连续（W/O）、油连续（O/W）和平衡微乳中的释放情况。对于分散相含量低的W/O和O/W配方，观察到DDA通过再生纤维素膜的线性扩散。在双连续制剂的情况下，药物释放曲线的非线性与更复杂的DDA分布有关，包括药物和载体之间的相互作用。随着水相浓度的增加，膜通量从25.02 μ g·cm ~（-2）·h ~（-1）（W/O微乳液）增加到117.94 μ g·cm ~（-2）·h ~（-1）（O/W微乳液）。此外，获得的平衡微乳液的通量值（29.38-63.70 μ g cm（-2）h（-1））表明双连续微结构阻碍两亲性药物的释放，（C）2005 Elsevier B. V.保留所有权利。
The Purpose of the present study was to determine the influence of both formulation parameters and vehicle structure on in vitro release rate of amphiphilic drug diclofenac diethylamine (DDA) from microemulsion vehicles containing PEG-8 caprylic/capric alycerides (surfactant), polyglyceryl-6 dioleate (cosurfactant), isopropyl myristate and water. From the constructed pseudoternary phase diagram at surfactant-cosurfactant mass ratio (K-m, 1: 1), the optimum oil-to-surfactant-cosurfactant mass ratio values (O/SC 0.67-1.64) for formulation of microemulsions with similar concentrations of hydrophilic, lipophilic and amphiphilic phases (balanced microemulsions) were found. The results of characterization experiments indicated bicontinuous or nonspherical water-continuous internal structure of the selected microemulsion vehicles. Low water/isopropyl myristate apparent partition coefficient for DDA as well as elevated electrical conductivity and apparent viscosity values for the investigated microemulsion formulations containing 1.16% (w/w) of DDA, suggested that the drug molecules was predominantly partitioned in the water phase and most likely selfaggregate and interact with interfacial film. Release of DDA from the selected water-continuous (W/O), oil-continuous (O/W) and balanced microemulsions was investigated using rotating paddle dissolution apparatus modified by addition of enhancer cell. A linear diffusion of DDA through regenerated cellulose membrane was observed for the W/O and O/W formulations with the low content of dispersed phase. Non-linearity of the drug release profile in the case of bicontinuous formulations was related to the more complex distribution of DDA including interactions between the drug and vehicle. The membrane flux value increases from 25.02 mu g cm(-2) h(-1) (W/O microemulsion) to 117.94 mu g cm(-2) h(-1) (O/W microemulsion) as the water phase concentration increases. Moreover, the obtained flux values for balanced microemulsions (29.38-63.70 mu g cm(-2) h(-1)) suggested that bicontinuous microstructure hampers the release of the amphiphilic drug, (C) 2005 Elsevier B.V. All rights reserved.