Non-degradable microparticles containing a hydrophilic and/or a lipophilic drug:: preparation, characterization and drug release modeling
Non-degradable microparticles containing a hydrophilic and/or a lipophilic drug:: preparation, characterization and drug release modeling
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DOI：
10.1016/s0168-3659(03)00030-0
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发表时间：
2003-03-26
影响因子：
10.8
通讯作者：
Maincent, P
中科院分区：
文献类型：
--
作者：
Hombreiro-Pérez, M;Siepmann, J;Maincent, P
采用水包油（O/W）和水包油包水（W/O/W）溶剂蒸发技术制备了含有亲水性药物盐酸普萘洛尔和/或亲脂性药物硝苯地平的甲基丙烯酸铵共聚物（Eudragit RS：RL 4：1共混物）的不可降解微粒。这两种药物分别和同时成功地结合在一起。在所有情况下，发现药物的最终释放速率在至少8小时的时间内得到控制。为了阐明潜在的质量传递机制，通过X-射线粉末衍射法、差示扫描量热法、粒度分析和实际载药量的测定来彻底表征微粒。考虑非稳态条件的菲克扩散第二定律的分析解被用来描述盐酸普萘洛尔的释放。有趣的是，发现与聚合物装置内的扩散阻力相比，微粒表面上的未搅拌液体边界层内的药物释放阻力可以忽略不计。重要的是，数学理论可用于相对于微粒尺寸标准化实验确定的体外药物释放。因此。可以研究制备方法的类型（O/W对W/O/W）和装置组成（聚合物共混物加仅一种药物对聚合物共混物加药物组合）对微粒内扩散阻力的影响。此外，对发生的质量传输过程有了进一步的了解。例如，可以计算暴露于释放介质时微粒内药物浓度曲线的时间依赖性演变。数学理论的一个有趣的实际应用是预测不同制剂参数对所得药物释放模式的影响的可能性。例如微粒尺寸的影响。(C)2003 Elsevier Science B. V.保留所有权利。
Non-degradable microparticles based on ammonio methacrylate copolymers (Eudragit RS:RL 4:1 blends) containing the hydrophilic drug propranolol HCl and/or the lipophilic drug nifedipine were prepared with an oil-in-xater (O/W) and a water-in-oil-in-water (W/O/W) solvent evaporation technique. Both drugs were successfully incorporated separately as well as simultaneously. In all cases, the resulting release rate(s) of the drug(s) was/were found to be controlled over periods of Lit least 8 h. To elucidate the underlying mass transport mechanisms, the microparticles were thoroughly characterized by X-ray powder diffractometry, differential scanning calorimetry, particle size analysis, and determination of the actual drug loading(s). Analytical solutions of Fick's second law of diffusion considering non-steady state conditions were used to describe the release of propranolol HCl. Interestingly, the resistance for drug release within the unstirred liquid boundary layers on the surfaces of the microparticles was found to be negligible compared to the diffusional resistance within the polymeric devices. Importantly, the mathematical theories could be used to normalize the experimentally determined in vitro drug release with respect to the microparticle size. Thus. the effect of the type of preparation method (O/W vs. W/O/W) and device composition (polymer blend plus one drug only vs. polymer blend plus drug combination) on the diffusional resistance within the microparticles could be studied. In addition, further insight into the occurring mass transport processes was gained. For example, the time-dependent evolution of the drug concentration profiles within the microparticles upon exposure to the release medium could be calculated. An interesting practical application of the mathematical theories is the possibility to predict the effect of different formulation parameters on the resulting drug release patterns. e.g. the effect of the microparticle size. (C) 2003 Elsevier Science B.V. All rights reserved.