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.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
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D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004285:Dogs; D007093:Imidazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D007441:Intubation, Gastrointestinal; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics
D003692:Delayed-Action Preparations; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; C029758:sulmazole