Emily C Ware1, D Robert Lu. 1. Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, USA.
Abstract
PURPOSE: The purpose of this study was to establish an automated approach to salt selection and to search for unique trazodone salts for new applications. METHODS: Automated procedures were developed on a Biomek 2000 automation workstation with stacker and plate reader capabilities. Trazodone was dispensed into 96-well plates, and an automated method was set up to form 104 trazodone salts. Salts were observed under a polarized light microscope to determine crystallinity. After stepwise eliminations, the remaining salts were scaled-up and subjected to differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), hygroscopic, pH-solubility, density, surface area, and particle size analyses. RESULTS: Oils formed in several cases resulting in preliminary elimination of mesyl and esyl salts and four crystallizing solvents. Crystallinity was observed in 34 of 44 scaled-up trazodone salts. PXRD, DSC, and hygroscopic analyses indicated a number of new salts that were comparable in physicochemical parameters to the marketed HCl salt. Among them, the tosylate salt showed uniqueness for new applications. CONCLUSIONS: Automated procedures can be developed to increase the efficiency of pharmaceutical salt selection. The new tosylate salt gave a unique pH-solubility profile with low solubility over the entire pH range making it a potential candidate for a suspension or prolonged action formulation.
PURPOSE: The purpose of this study was to establish an automated approach to salt selection and to search for unique trazodone salts for new applications. METHODS: Automated procedures were developed on a Biomek 2000 automation workstation with stacker and plate reader capabilities. Trazodone was dispensed into 96-well plates, and an automated method was set up to form 104 trazodone salts. Salts were observed under a polarized light microscope to determine crystallinity. After stepwise eliminations, the remaining salts were scaled-up and subjected to differential scanning calorimetry (DSC), powder x-ray diffraction (PXRD), hygroscopic, pH-solubility, density, surface area, and particle size analyses. RESULTS: Oils formed in several cases resulting in preliminary elimination of mesyl and esyl salts and four crystallizing solvents. Crystallinity was observed in 34 of 44 scaled-up trazodone salts. PXRD, DSC, and hygroscopic analyses indicated a number of new salts that were comparable in physicochemical parameters to the marketed HCl salt. Among them, the tosylate salt showed uniqueness for new applications. CONCLUSIONS: Automated procedures can be developed to increase the efficiency of pharmaceutical salt selection. The new tosylate salt gave a unique pH-solubility profile with low solubility over the entire pH range making it a potential candidate for a suspension or prolonged action formulation.
Authors: Peter A Bell; Surendra Chaturvedi; Craig A Gelfand; Ching Yu Huang; Michael Kochersperger; Rafael Kopla; Frank Modica; Mark Pohl; Shobha Varde; Renbin Zhao; Xiaojian Zhao; Michael T Boyce-Jacino; Azzam Yassen Journal: Biotechniques Date: 2002-06 Impact factor: 1.993
Authors: Alexander Alanine; Matthias Nettekoven; Edward Roberts; Andrew W Thomas Journal: Comb Chem High Throughput Screen Date: 2003-02 Impact factor: 1.339