title: Co-amorphous Formation Induced by Combination of Tranilast and Diphenhydramine Hydrochloride.
abstract: 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.
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan; Physicochemical and Preformulation, Applied Chemistry and Analysis, Research Laboratory for Development, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan; Physicochemical and Preformulation, Applied Chemistry and Analysis, Research Laboratory for Development, Shionogi & Co., Ltd., Toyonaka, Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Imono
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ito
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Kunita
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan. Electronic address: ytozuka@gly.oups.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
mesh_terms: D018926:Anti-Allergic Agents / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004155:Diphenhydramine / Q000737:chemistry*; D004338:Drug Combinations; D013816:Thermodynamics; D044366:Transition Temperature; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D018926:Anti-Allergic Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D062367:ortho-Aminobenzoates; D004155:Diphenhydramine; C012293:tranilast
keywords: amorphous; co-amorphous; crystallization; enthalpy relaxation; glass transition temperature; intermolecular interaction