원보 ; 오메프라졸복합체 함유 직장좌제의 특성비교 = Original Articles ; A Comparative Study on the Pharmaceutical Properties of Rectal Suppository containing Omeprazole Complexes

다국어 초록 (Multilingual Abstract)

Omeprazole(OMP) complexes such as inclusion complexes of OMP with hydroxypropyl-β-cyclodextrin(HPCD) and β-cyclodextrin(β-CD), OMP-cholestyramine(CHL) and OMP-ethylenediamine(OMP-ED) were prepared, respectively. The partition coefficients in Witepsol H-15/pH 7.4 phosphate buffer solution of OMP complexes(OMP-HPCD: 3.69±0.26, OMP-β-CD: 4.08±0.21, OMP-CHL: 4.36±0.25 and omeprazole sodium(OMP-Na): 3.64±0.37) were higher than that of OMP (2.66±0.47). OMP was not completely dissolved until even 3 hrs, but all the OMP complexes studied were released about 100% in 20 min. The rectal suppositories containing OMP or each above OMP complex were prepared using Witepsol H-15 base, and their dissolution and stability were examined, and pharmacokinetic study were investigated after their rectal ad ministrations to the rabbits. While the suppository containing OMP was released only less than 60% in 150 min, OMP-β-CD, OMP-CHL, OMP-Na and OMP-ED suppositories were all released about 65% in 20 min. Especially, OMP-HPCD suppository released OMP about 70% in 10 min. All the additives such as sodium laurylsulfate, eglumine, arginine and PVP increased drug release from OMP-HPCD suppository to some extent. The decomposition rate constants of OMP in the suppositories were 9.117×10^(-3) day^(-1) for OMP suppository, 2.121×10^(-2) for OMP-HPCD. 1. 607×10^(-2) for OMP-β-CD, 9.26×10^(-3) for OMP-Na. 6.769×10^(-3) for OMP-CHL and 5.58×10^(-3) day^(-1) for OMP-ED suppository, respectively. Additives such as arginine, eglumine and ED had some stabilizing effect for OMP-HPCD, OMP-CHL and OMP-Na suppositories, respectively. After 6 month-storage at 30℃. 75% RH, OMP-CHL suppository was most stable. The values of Tmax for OMP-HPCD and OMP-Na suppositories were 11.7±2.36 and 11.4±2.56 min, respectively. The values of Cmax for OMP-HPCD and OMP-CHL suppository were 2.31 ㎍/㎖ (p<0.01) and 1.89 ㎍/㎖ p<0.01), respectively. The values of AUC for OMP and OMP-β-CD suppository were 61.9±25.79 and 68.6±29.48 ㎍·min/㎖, and the corresponding values for OMP-HPCD and OMP-CHL were 106.1±43.16 (p<0.05) and 127.3±42.52 ㎍·min/㎖(p<0.01), respectively. The above results indicate the OMP-HPCD and OMP-CHL suppositories have the excellent bioavailabilities in vivo study.