An automated approach to salt selection for new unique trazodone salts.
Pharm Res
; 21(1): 177-84, 2004 Jan.
Article
em En
| MEDLINE
| ID: mdl-14984273
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sais
/
Trazodona
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2004
Tipo de documento:
Article