Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylamine derivative for oral administration at an exploratory stage of new drug development

Preliminary preformulation studies of a 2-(3,4-dimethoxyphenyl)ethylamine derivative were investigated. The hydrochloride form showed incompatibility with the excipients used for oral dosage forms. There were several crystal forms of the free base, namely, alpha-anhydrate, beta-anhydrate, monohydrate, and trihydrate. The trihydrate form was unstable. The degree of crystallinity of the beta-anhydrate form was difficult to control. The monohydrate form was difficult to manufacture with constant 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. However, the dissolution rates from the formulations of alpha-anhydrate were improved. After oral administration of the improved formulation, the serum level of alpha-anhydrate in beagle dogs was almost triple that after the oral administration of the capsule of the hydrochloride form.