Insights into Water-Induced Phase Separation in Itraconazole–Hydroxypropylmethyl Cellulose Spin Coated and Spray Dried Dispersions,Molecular Pharmaceutics

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Insights into Water-Induced Phase Separation in Itraconazole–Hydroxypropylmethyl Cellulose Spin Coated and Spray Dried Dispersions
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2017-11-08 00:00:00 , DOI: 10.1021/acs.molpharmaceut.7b00499
Naila A. Mugheirbi ₁ , Patrick J. Marsac ₂ , Lynne S. Taylor ₁

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For amorphous solid dispersions, understanding the phase behavior of a given drug–polymer blend and factors that influence miscibility is crucial to designing an optimally performing formulation. However, it can be challenging to fully map the phase behavior of some systems, especially those produced using a cosolvent system. In this study, a comprehensive investigation of phase separation in itraconazole–hydroxypropylmethylcellulose (ITZ–HPMC) blends fabricated using solvent evaporation processes, including spin coating and spray drying, has been carried out. Phase separation was found to be driven by the presence of water, either acquired from the environment or from the solvent system. ITZ nanospecies were observed during the solvent evaporation process prior to solidification. The use of high resolution imaging techniques such as transmission electron microscopy including bright field and high angle annular dark field imaging, enabled detailed characterization of the microstructure of phase separated systems. Spectroscopic investigations suggested that drug domains contain supramolecular drug aggregates in which the nematic assembly of ITZ molecules results in the coupling of the optical transitions of ITZ monomers. Importantly, a similar pattern of behavior between drug–polymer phase in spin coated and spray dried dispersions was observed. The presence of as little as 1% water in the solvent was found to induce phase separation in the spray dried particles, which was detected using the unique photophysical properties of ITZ and fluorescence spectroscopy. The study highlights the complexity of drug–polymer phase behavior and the influence of solvent properties.

中文翻译：

伊曲康唑-羟丙基甲基纤维素旋涂和喷雾干燥分散液中水诱导相分离的见解

对于无定形固体分散体，了解给定药物-聚合物混合物的相行为以及影响溶混性的因素对于设计最佳性能的配方至关重要。但是，要完全绘制某些系统的相行为，尤其是使用共溶剂系统生产的系统，可能会面临挑战。在这项研究中，已经对使用溶剂蒸发工艺（包括旋涂和喷雾干燥）制得的伊曲康唑-羟丙基甲基纤维素（ITZ-HPMC）共混物中的相分离进行了全面研究。发现相分离是由水的存在驱动的，水的存在是从环境或从溶剂系统获得的。在固化之前的溶剂蒸发过程中观察到ITZ纳米物种。高分辨率成像技术的使用，例如透射电子显微镜，包括亮场和高角度环形暗场成像，可以对相分离系统的微观结构进行详细表征。光谱研究表明，药物结构域包含超分子药物聚集体，其中ITZ分子的向列组装导致ITZ单体光学跃迁的耦合。重要的是，在旋涂和喷雾干燥的分散体中，药物-聚合物相之间的行为模式相似。发现溶剂中少至1％的水会导致喷雾干燥的颗粒发生相分离，这是使用ITZ独特的光物理性质和荧光光谱法检测到的。

更新日期：2017-11-08

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