Optimization of Hot-Melt Extrusion Processing for the Synthesis of Ionic Cocrystals

IF 3.2 2区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY Crystal Growth & Design Pub Date : 2023-09-18 DOI:10.1021/acs.cgd.3c00773
Dunja Šilić, Biserka Cetina-Čižmek, Steven A. Ross, Andrew Hurt, Milan Antonijevic and Dennis Douroumis*, 
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Abstract

Cocrystals are multicomponent crystalline forms that are an appealing alternative to modify undesirable properties of drug substances, such as poor solubility and stability. Hot-melt extrusion (HME), a solvent-free, robust, and scalable technology, has been proven to be a suitable approach for cocrystallization of several drug-coformer pairs. However, HME has been mainly implemented for the synthesis of molecular cocrystals when most of the marketed products are manufactured in the form of ionic cocrystals. In this study, the synthesis of extruded fluoxetine HCl-succinic acid cocrystals was investigated using different screw configurations. Ionic cocrystals manufactured by HME showed complete transformation of the drug-coformer pair with high purity, improved intrinsic dissolution rates, and long-term storage stability when compared to their counterparts produced by solvent evaporation.

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离子共晶合成的热挤压工艺优化
共晶是多组分结晶形式,是改变药物不良性质(如溶解性和稳定性差)的一种有吸引力的替代品。热熔挤出(HME)是一种无溶剂、稳健且可扩展的技术,已被证明是几种药物共形成剂对共结晶的合适方法。然而,当大多数市场上的产品以离子共晶的形式生产时,HME主要用于合成分子共晶。在本研究中,研究了使用不同的螺旋构型合成挤出的氟西汀-盐酸-琥珀酸共晶。与溶剂蒸发产生的离子共晶相比,HME制造的离子共晶体显示出药物共形成物对的完全转化,具有高纯度、改进的固有溶解速率和长期储存稳定性。
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来源期刊
Crystal Growth & Design
Crystal Growth & Design 化学-材料科学:综合
CiteScore
6.30
自引率
10.50%
发文量
650
审稿时长
1.9 months
期刊介绍: The aim of Crystal Growth & Design is to stimulate crossfertilization of knowledge among scientists and engineers working in the fields of crystal growth, crystal engineering, and the industrial application of crystalline materials. Crystal Growth & Design publishes theoretical and experimental studies of the physical, chemical, and biological phenomena and processes related to the design, growth, and application of crystalline materials. Synergistic approaches originating from different disciplines and technologies and integrating the fields of crystal growth, crystal engineering, intermolecular interactions, and industrial application are encouraged.
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