An automated approach to salt selection for new unique trazodone salts.
OBJECTIVE
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.
Ware
Emily C
EC
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, Georgia 30602, USA.
Lu
D Robert
DR
D006863:Hydrogen-Ion Concentration; D010316:Particle Size; D011208:Powders; D012492:Salts / Q000032:analysis / Q000737:chemistry*; D012995:Solubility; D014196:Trazodone / Q000032:analysis / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
D011208:Powders; D012492:Salts; D014196:Trazodone