PRELIMINARY PREFORMULATION STUDIES OF A 2-(3,4-DIMETHOXYPHENYL)ETHYLAMINE DERIVATIVE FOR ORAL-ADMINISTRATION AT AN EXPLORATORY STAGE OF NEWDRUG DEVELOPMENT

Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylam ine derivative were investigated. The hydrochloride form showed incomp atibility with the excipients used for oral dosage forms. There were s everal crystal forms of the free base, namely, alpha-anhydrate, beta-a nhydrate, monohydrate, and trihydrate, The trihydrate form was unstabl e, The degree of crystallinity of the beta-anhydrate form was difficul t to control, The monohydrate form was difficult to manufacture with c onstant quality. The serum levels of the compounds in rats were almost related to the dissolution rates in the JP 1st disintegration medium from the discs. The serum level of alpha-anhydrate was the lowest. How ever, the dissolution rates from the formulations of alpha-anhydrate w ere improved, After oral administration of the improved formulation, t he serum level of alpha-anhydrate in beagle dogs was almost triple tha t after the oral administration of the capsule of the hydrochloride fo rm.