Co-amorphous Formation Induced by Combination of Tranilast and Diphenhydramine Hydrochloride

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• 作者：Hiroshi Ueda¹ ; ² ; Kazunori Kadota¹ ; Masaaki Imono¹ ; ² ; Takuya Ito¹ ; Ayaka Kunita¹ ; Yuichi Tozuka¹ ; ^{ytozuka@gly.oups.ac.jp}
• 关键词：amorphous ; co-amorphous ; glass transition temperature ; enthalpy relaxation ; intermolecular interaction ; crystallization
• 刊名：Journal of Pharmaceutical Sciences
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：106
• 期：1
• 页码：123-128
• 全文大小：852 K
• 卷排序：106

文摘

In this study, we investigated the formation of a co-amorphous system of tranilast (TRL) and diphenhydramine hydrochloride (DPH), which are drugs used for treating allergies and inflammation. The crystallization from undercooled melts of the drugs and drug mixtures was evaluated by thermal analysis. Both drugs in the amorphous state underwent crystallization on heating, although the mixture remained in the amorphous state, indicating the formation of a co-amorphous system. The physicochemical properties of co-amorphous TRL-DPH prepared by the melting-cooling process were studied. The glass transition temperature of co-amorphous TRL-DPH deviated from the theoretical value. The enthalpy relaxation rate of the amorphous drugs, which reflected the molecular mobility, was reduced by the formation of a co-amorphous system. The intermolecular interactions between TRL and DPH in the co-amorphous system were measured by the change in the IR spectra. These results were consistent with the high physical stability. The co-amorphous sample remained in the amorphous state for over 30 days at 40°C, whereas the amorphous drugs showed rapid crystallization. Our findings demonstrate that TRL and DPH form a co-amorphous system, which dramatically decreases their crystallization without an excipient.