Résumé
OBJECTIVE: To prepare compound aspirin and esomeprazole magnesium enteric-coated pellet capsules and evaluate the drug release in vitro/in vivo. METHODS: The aspirin pellet cores were prepared by using extrusion-spheronization method, and the esomeprazole magnesium-containing drug pellets were prepared with fluidized bed. By using fluidized bed coating method, the two kinds of drug-containing pellets were respectively coated with enteric layer to obtain enteric-coated pellets. After determining the loading capacity by measuring drug content, the two kinds of drug-containing pellets were filled into No.1 capsules. In vitro release was evaluated by measuring release percentage. The in vivo release behavior was evaluated by determination of pharmacokinetic parameters in rats. RESULTS: The cumulative release percentage of the two drugs was less than 5% in 2 h in 0.1 mol·L-1 hydrochloric acid solution. The cumulative release percentage of aspirin was more than 70% in 45 min in pH 6.8 PBS and it was more than 80% in 30 min for esomeprazole magnesium. Aspirin was metabolized to salicylic acid in plasma and its main pharmacokinetic parameters were as follows:t1/2=9.47 h, MRT0-∞=14.43 h, tmax=3.00 h, ρmax=51.34 mg·L-1, AUC0-24=703.39 mg·h·L-1, AUC0-∞=860.52 mg·h·L-1. The pharmacokinetic parameters for esomeprazole magnesium were as follows:t1/2=3.72 h, MRT0-∞=7.44 h,tmax=1.50 h, ρmax=2.71 mg·L-1, AUC0-24=11.89 mg·h·L-1, AUC0-∞=13.79 mg·h·L-1. CONCLUSION: The formulation of compound enteric-coated pellet capsules is reasonable, and the preparation technology has good reproducibility. The drug release is located in the intestinal tract, thus esomeprazole magnesium can antagonize the gastrointestinal side effects of aspirin and aspirin can produce better antithrombotic effect.