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

• Published in: Journal of pharmaceutical sciences Vol. 106; no. 1; pp. 123 - 128
• Main Authors: Ueda, Hiroshi, Kadota, Kazunori, Imono, Masaaki, Ito, Takuya, Kunita, Ayaka, Tozuka, Yuichi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2017
• Subjects: amorphous; Anti-Allergic Agents - chemistry; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Calorimetry, Differential Scanning; co-amorphous; Crystallization; Diphenhydramine - chemistry; Drug Combinations; enthalpy relaxation; glass transition temperature; intermolecular interaction; ortho-Aminobenzoates - chemistry; Thermodynamics; Transition Temperature; amorphous; intermolecular interaction; XRPD; glass transition temperature; enthalpy relaxation; co-amorphous; tc; TRL; Tg; DSC; crystallization; Tm; DPH; PM
• ISSN: 0022-3549; 1520-6017; 1520-6017
• DOI: 10.1016/j.xphs.2016.07.009

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.