Omeprazole(OMP) complexes such as inclusion complexes of OMP with hydroxypropyl-β-cyclodextrin(HPCD) and β-cyclodextrin(β-CD).OMP-cholestyramine(CHL) and OMPethylenediamine(OMP-ED) were prepared, respectively. The partition coefficients in
Witepsol
H15/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 was examined, and
pharmacokinetic
study were investigated after their rectal administrations 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, resepctively. The values of Cmax for OMP-HPCD and OMP-CHL suppository were 2.31㎍/ml (p<0.01) and 1.89㎍/ml 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/ml, and the corresponding values for OMP-HPCD and OMP-CHL were 106.1±43.16(p<0.05) and 127.3±45.52㎍.min/ml(p<0.01), respectively. The above results indicate the OMP-HPCD and OMP-CHL suppositories have the excellent bioavailabilties in vivo
study.
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