The object of the study was to develop an oral dosage form of aminorex which would produce prolonged, stable plasma levels of total drug. Since no definite set of dissolution conditions exists for the evaluation of the in uiuo availability of a given drug, an arbitrary set of dissolution conditions was chosen. A priori it was assumed that a correlation existed between in uifro dissolution and in uiuo availability. If this were true, changes in dosage form release characteristics could be evaluated in uirro before going to man. In viuo availability was determined in human subjects, by determination of total plasma radioactivity following administration of aminorex-W. Several of the subjects were crossed over from one dosage form to another. Good correlation was obtained between in citro dissolution and in uiuo absorption rates. In uioo absorption rates of intact drug were calculated from the plasma data for total radioactivity. A one-compartment open model was used to describe the system. Dosage forms which produced prolonged blood levels of radioactivity were found to give prolonged clinical response.
Keyphrases
Sustained-release dosage f~rms-aminorex-~~C 0 Aminorex-14C dosage forms-in vitro dissolution rates, correlation in uiuo availability 0 Kinetic analy~is-aminorex-~~C absorption, elimination 0 Model, one-compartment-drug absorption 0 Scintillometry-analysis During the course of the development of a new nonamphetamine anorexigenic agent, aminorex, it was decided t o examine the possibility of once a day dosage. ~ * All data were obtained from the average plasma level curves of Figs. 2 and 3 using the half-life of 7.7 hr, obtained for dosage forms A and B. * No value for ( F / V ) m was calculated due to the existence of a maximum in the A t / V plot for this dosage form. See text for explanation.