Miscibility of Itraconazole鈥揌ydroxypropyl Methylcellulose Blends: Insights with High Resolution Analytical Methodologies

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• 作者：Hitesh S. Purohit ; Lynne S. Taylor
• 刊名：Molecular Pharmaceutics
• 出版年：2015
• 出版时间：December 7, 2015
• 年：2015
• 卷：12
• 期：12
• 页码：4542-4553
• 全文大小：709K
• ISSN：1543-8392

文摘

Drug鈥損olymer miscibility is considered to be a prerequisite to achieve an optimally performing amorphous solid dispersion (ASD). Unfortunately, it can be challenging to evaluate drug鈥損olymer miscibility experimentally. The aim of this study was to investigate the miscibility of ASDs of itraconazole (ITZ) and hydroxypropyl methylcellulose (HPMC) using a variety of analytical approaches. The phase behavior of ITZ-HPMC films prepared by solvent evaporation was studied before and after heating. Conventional methodology for miscibility determination, that is, differential scanning calorimetry (DSC), was used in conjunction with emerging analytical techniques, such as fluorescence spectroscopy, fluorescence imaging, and atomic force microscopy coupled with nanoscale infrared spectroscopy and nanothermal analysis (AFM-nanoIR-nanoTA). DSC results showed a single glass transition event for systems with 10% to 50% drug loading, suggesting that the ASDs were miscible, whereas phase separation was observed for all of the films based on the other techniques. The AFM-coupled techniques indicated that the phase separation occurred at the submicron scale. When the films were heated, it was observed that the ASD components underwent mixing. The results provide new insights into the phase behavior of itraconazole鈥揌PMC dispersions and suggest that the emerging analytical techniques discussed herein are promising for the characterization of miscibility and microstructure in drug鈥損olymer systems. The observed differences in the phase behavior in films prepared by solvent evaporation before and after heating also have implications for processing routes and suggest that spray drying/solvent evaporation and hot melt extrusion/melt mixing can result in ASDs with varying extent of miscibility between the drug and the polymer.