Physicochemical properties of amorphous salt of cimetidine and diflunisal system.
The purpose of this study was to prepare amorphous precipitates of the binary system of cimetidine (CIM) and diflunisal (DIF) and to investigate the physicochemical properties of the precipitates. To achieve this, the interaction between CIM and DIF molecules was studied by means of nuclear magnetic resonance (NMR) and Fourier-transform infrared (FTIR) measurements. The binary system of CIM and DIF was found to become amorphous upon precipitation from ethanol solution, without heating or melting. In the thermal analysis by TG-DTA equipped with a mass spectrometer, decarboxylation of DIF was found to occur below its melting temperature. In NMR studies, the chemical shifts of a proton in the imidazole ring of CIM and the carbon to which the DIF carboxyl group is bound were found to change depending on the composition of the binary system. The change in NMR chemical shifts suggested that a salt was formed between CIM and DIF. The precipitates had higher solubility than intact drugs due to this salt formation. The results suggest that CIM may be useful as an amorphous carrier, without requiring heating or melting, due to the formation of a salt with acidic drugs.
Yamamura
Shigeo
S
School of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan. yamamura@phar.toho-u.ac.jp
Gotoh
Hiroaki
H
Sakamoto
Yohko
Y
Momose
Yasunori
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000737:chemistry*; D004061:Diflunisal / Q000737:chemistry*; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D004061:Diflunisal; D002927:Cimetidine