Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers
Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers
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DOI：
10.1016/j.ejpb.2006.07.007
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发表时间：
2007-01-01
影响因子：
4.9
通讯作者：
Singh, Bhupinder
中科院分区：
文献类型：
--
作者：
Ahuja, Naveen;Katare, Om Prakash;Singh, Bhupinder
采用固体分散法研究了不同水溶性载体对难溶性模型药物罗非昔布溶出的促进作用。为此目的，研究了不同的载体，即聚乙二醇（PEG 4000和6000）、聚乙二醇化脂肪酸酯（Gelucire（R）44/14）、聚乙烯吡咯烷酮K25（PVP）、泊洛沙姆（Lutrol（R）F127和F68）、多元醇（甘露醇、山梨醇）、有机酸（柠檬酸）和水溶助长剂（脲、烟酰胺）。相溶解度研究揭示了每种载体的A（L）型曲线，表明药物溶解度随载体浓度线性增加。热力学参数吉布斯自由能的符号和大小表明增溶过程的自发性。与纯药物维斯，所有固体分散体均表现出不同程度的溶出改善，其中柠檬酸、PVP和泊洛沙姆是最有前途的载体。体外溶出数据的数学模型表明，最好的拟合Korsemeyer-Peppas模型和药物释放动力学主要为菲克扩散。使用XRD、FTIR、DSC和SEM技术对药物-泊洛沙姆二元体系的固态表征揭示了制剂中药物结晶度的明显损失，表面上解释了溶出速率的增强。(c)2006 Elsevier B. V.保留所有权利。
Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire (R) 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol (R) F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed A(L) type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-A-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate. (c) 2006 Elsevier B.V. All rights reserved.