Uji Efek Analgetik dan Keamanan terhadap Lambung dari Aspirin yang Diberikan dengan Cangkang Kapsul Alginat pada Kelinci

Abstract

The administration of aspirin in shell of gelatin capsule caused an local irritation on gastrointestinal (GI) tract, particularly on stomach. In this study, aspirin in shell of alginate capsule was administrated to rabbits for avoiding local irritation side effect on stomach. The comparison between shell of gelatin capsule and shell of alginate capsule on in vitro dissolution bioavailability, analgesic effect and irritation effect of aspirin were done in this study. The dissolution of aspirin from shell of alginate capsule and shell of gelatin capsule was tested by using paddle method in continuous pH change medium i.e. 1.2:4.5; and 6.8. Then the concentration of aspirin was determined by using ultaviolet spectrophotometer. The bioavailabitity of aspirin was performing using rabbits, and the salicylate and aspirin concentrations in the plasma were determine by using visible spectophotometer. The analgesic effect of aspirin was tested using rabbits by 2 methods, i,e. determination of temperature (oC) at which respond begun, and determination of duration of respond at 49oC. The irritation effect of aspirin on GI tract was chronically tested for 3 months (90 day). The dose of aspirin used in the in vitro dissolution test was 80 mg. The dose of aspirin used in the in vivo bioavailability, analgesic, and irritation tests was 80 mg/rabbit for single dose. The results of this experiment showed that the dissolution rate of aspirin in medium pH 1.2 from shell of alginate capsule was slower than that of aspirin from shell of gelatin capsule. Aspirin in shell of alginate capsule and shell of gelatin capsule was bioequivalent in Cmax parameter, while AUC in shell of alginate capsule was larger than AUC in shell of gelatin capsule, and tmax of aspirin in shell of alginate capsule was longer than tmax of aspirin in shell of gelatin capsule. The value of Cmax, AUC, tmax of salicylate acid as aspirin's metabolite in plasma of rabbits which was administrated aspirin in shell of gelatin capsule were 53.2880 mcg/ml; 184.9224 hours.mcg/ml; 160 minutes, respectively. But the other one which was administrated shell of alginate capsule were 55.4138 mcg/ml; 202.5227 hours.mcg/ml; 250 minutes, respectively. The value of Cmax, AUC, tmax of salicylate and aspirin in plasma of rabbits received in shell of gelatin capsule were 101.3322 mcg/ml; 395.2842 hours.mcg/ml; 160 minutes, respectively. However, administrated with shell of alginate capsule were 107.001 1 mcg/ml; 527.4589 hours.mcg/ml; 250 minutes, respectively, the value of Cmax , AUC, tmax of aspirin in plasma of rabbits in shell of gelatin capsule were 62.6676 mcg/ml; 274.3902 hours.mcg/ml; 160 minutes, respectively. But the other one which was administrated with shell of alginate capsule were 67.2891 mcg/ml; 423.8380 hours.mcg/ml; 250 minutes, respectively. The analgesic effect of aspirin in shell of gelatin capsule and alginate capsule was not significantly differet at p=0.05. The chronic irritation test observed for 3 months (90 days) showed that the aspirin in shell of alginate capsule caused no irritation on rabbits GI tract gaster. In contrast, the aspirin in shell gelatin capsule caused irritation on rabbit's stomach, and it was not found irritation on intestinal and colon of rabbits.