A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties
A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties
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DOI：
10.1016/j.ijpharm.2016.01.006
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发表时间：
2016-02-29
影响因子：
5.8
通讯作者：
Halbert, Gavin W.
中科院分区：
文献类型：
--
作者：
Martinez-Marcos, Laura;Lamprou, Dimitrios A.;Halbert, Gavin W.
研究的主要目的集中在生产热熔挤出（HME）制剂，提高阿苯达唑（ABZ）的溶解性能。因此，HME作为连续生产技术应用于生产与聚合物基质聚乙烯吡咯烷酮PVP K12组合的水溶性差的药物ABZ的无定形固体分散体。ABZ-PVP K12的HME制剂包含1%、5%和10%w/w的药物含量。使用的主要分析表征技术为扫描电子显微镜（SEM）、微型计算机断层扫描（mu-CT）、X射线粉末衍射（XRPD）、差示扫描量热法（DSC）和溶出曲线研究。SEM、XRPD和DSC的应用证明了药物从结晶到无定形的物理转化，从而实现了无定形固体分散体。引入一种新的技术，mu-CT，来分析这些材料的内部结构，揭示了有关材料分布和空隙含量的关键信息。溶出曲线研究表明，与纯ABZ相比，药物释放曲线大幅增加。这些有希望的结果可以导致ABZ剂型的口服生物利用度的极大提高。因此，HME是一种潜在的连续生产技术，可克服ABZ溶解度差的特性，并显著提高治疗效果。(C)2016爱思唯尔B. V.保留所有权利。
The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (mu-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, mu-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect. (C) 2016 Elsevier B.V. All rights reserved.