Binary polymeric blends to microencapsulate nitroflurbiprofen: Physicochemical and in silico studies
Binary polymeric blends to microencapsulate nitroflurbiprofen: Physicochemical and in silico studies
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DOI：
10.1016/j.ejps.2007.03.010
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发表时间：
2007-07-01
影响因子：
4.6
通讯作者：
Montanari, Luisa
中科院分区：
文献类型：
--
作者：
Cilurzo, Francesco;Selmin, Francesca;Montanari, Luisa
将硝基氟比洛芬（NFP）（一种几乎不溶的液体药物）微胶囊化在由聚（N-乙烯基吡咯烷酮）（PVP）或聚氨基甲基丙烯酸酯（PAMA）或其聚合物的二元共混物制成的亲水性微基质中。在过饱和条件下进行NFP体外释放试验，以区分NFP表观溶解度（过饱和度，SD）的增加。药物/聚合物/聚合物/水相互作用通过分子动力学（MD）模拟在计算机上进行了研究。PAMA和PVP仅在水溶液中混溶。由于不稳定的过饱和体系的形成和药物在溶出介质中的分离，NFP从微粒中的释放按照非单调模式发生。5分钟后，SD至少为3。PVP/PAMA微基质的使用降低了过饱和溶液的不稳定性。分子动力学模拟表明，水分子在PAMA/PVP增容过程中起着关键作用，并通过氢键稳定NFP过饱和体系。对接分析在这里找到一个新的和成功的应用，预测不同的药物相互作用的能力与聚合物共混物在溶液中。(c)2007 Elsevier B. V.保留所有权利。
Nitroflurbiprofen, NFP, a practically insoluble liquid drug, was microencapsulated in hydrophilic micromatrices made of poly(N-vinylpyrrolidone) (PVP), or polyaminomethacrylate (PAMA), or binary blends of polymers thereof.The PAMA/PVP miscibility was assessed both in the solid state (DSC and ATF-FTIR spectroscopy) and in solution by viscometric measurements. The in vitro NFP release test was carried out in over saturation condition to discriminate the increase of NFP apparent solubility (supersaturation degree, SD). Drug/polymer/polymer/water interactions were studied in silico by molecular dynamic (MD) simulations. PAMA and PVP resulted miscible only in aqueous solution. The release of NFP from microparticles occurred according to a non-monotonic pattern due to the formation of instable supersaturated systems and the drug separation in the dissolution medium. After 5 min, the SD was at least 3. The use of PVP/PAMA micro-matrices reduced the instability of the supersaturated solutions. MD simulations evidenced that water molecules play a key role in the PAMA/PVP compatibilization process and in stabilization of NFP supersaturated systems by means of H-bond. The docking analyses here find a novel and successful application to predict the different ability of a drug to interact with polymeric blends in solution. (c) 2007 Elsevier B.V. All rights reserved.