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Sustained release of isomazole from matrix tablets administered to dogs.

Isomazole matrix tablet formulations, with various concentrations of hydroxypropyl methylcellulose (HPMC) hydrogel, were prepared and tested for sustained-release activity. Sustained-release activity was determined by administering isomazole test formulations orally to conscious dogs, instrumented with an indwelling left ventricular pressure transducer, and monitoring cardiac inotropic changes for 12 h thereafter. The HPMC hydrogel incorporated into the tablets at a concentration of 20-30% did not significantly change the magnitude of inotropic response or duration of action. Increasing the HPMC concentration to 40 and 42.5% in the formulations decreased the peak LVdP/dt60 response (cardiac inotropic activity) to isomazole, increased the response duration, and maintained the area under the curve (AUC) of LVdP/dt60 versus time. Higher concentrations of HPMC decreased both LVdP/dt60 peak activity and AUC without producing a sustained response. A very narrow range of HPMC concentration in the matrix tablet is thus required to achieve isomazole sustained-release activity.