title: Molecular salts and co-crystals of mirtazapine with promising physicochemical properties.
abstract: Pharmaceutically suitable non-sublimating salts and molecular salts of anti-depressant drug R/S-mirtazapine with one of several dicarboxilic acids were studied. The salts/salt molecules were characterized by powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis and crystal structure of tartarate and oxalate molecular salt were determined by single crystal X-ray diffraction. The salts/salt molecules of mirtazapine do not show any sublimation at elevated temperature whereas sublimation of mirtazapine has been observed at ambient temperature. The aqueous solubility of the mirtazapine molecular salts was significantly improved with a maximum of citrate salt which was about 180 times more than the solubility of the parent mirtazapine at 35 °C.
authors.affiliation: Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON, Canada N6A 5B9.
authors.forename: Anindita
authors.initials: A
authors.lastname: Sarkar
authors.affiliation: Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, ON, Canada N6A 5B9. Electronic address: srohani@uwo.ca.
authors.forename: Sohrab
authors.initials: S
authors.lastname: Rohani
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002951:Citrates / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D003998:Dicarboxylic Acids / Q000737:chemistry*; D007700:Kinetics; D008803:Mianserin / Q000031:analogs & derivatives* / Q000737:chemistry; D000078785:Mirtazapine; D008958:Models, Molecular; D015394:Molecular Structure; D010070:Oxalates / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D013644:Tartrates / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013818:Thermogravimetry; D014867:Water / Q000737:chemistry
chemical_list: D000929:Antidepressive Agents, Tricyclic; D002951:Citrates; D003998:Dicarboxylic Acids; D010070:Oxalates; D013644:Tartrates; D014867:Water; D008803:Mianserin; D000078785:Mirtazapine
keywords: Aqueous solubility; Mirtazapine salts; Molecular salt; Non-sublimating salts; Single crystal structure