Effect of adsorbents on the absorption of lansoprazole with surfactant
Abstract
Lansoprazole (LPZ) is a representative drug that shows a high inter-subject variation of bioavailability (BA). Solid preparation composed of surfactant, adsorbent and LPZ were prepared to improve the dissolution and absorption of LPZ, and the BA of LPZ was measured in rats and dogs. As surfactant, Tween 80, polyoxy 60 hydrogenated caster oil derivative (HCO-60) and PEG-8 caprylic/capric glycerides (Labrasol) were used. As adsorbant, porous silicon dioxide (Sylysia 550, 320), magnesium aluminometa silicate (Neusilin S2, NS2N, US2) and porous calcium silicate (Florite RE) were used. After small intestinal administration of LPZ, 5.0 mg/kg, solution with HCO-60 showed the highest plasma LPZ concentration versus time curve of which C(max) and AUC was 0.46+/-0.01 microg/mL and 0.73+/-0.03 microgh/mL. By comparing to that after i.v. injection of LPZ solution, 2.0 mg/kg, the BA of LPZ from HCO-60 solution was 39.0%, which was about seven times higher than that of LPZ powder. To solidify the LPZ solution with HCO-60, adsorbents were used and the obtained solid preparations were used for in vitro release experiment. Sylysia 320, Neusilin S2 and Neusilin NS2 showed the T50% of about 1h. To evaluate the BA of these solid preparations, absorption study was performed in rats. Sylysia 550 system showed the higher AUC than other systems, showing the BA of 28.1%. Sylysia 550 system was filled in an enteric capsule and was orally administered to dogs and BA was compared with enteric tablet.…
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