Effect of adsorbents on the absorption of lansoprazole with surfactant
Effect of adsorbents on the absorption of lansoprazole with surfactant
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DOI：
10.1016/j.ijpharm.2004.10.010
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发表时间：
2005-01-31
影响因子：
5.8
通讯作者：
Takada, K
中科院分区：
文献类型：
--
作者：
Ito, Y;Arai, H;Takada, K
兰索拉唑（LPZ）是生物利用度（BA）受试者间差异较大的代表性药物。制备了表面活性剂、吸附剂和LPZ组成的固体制剂，以提高LPZ的溶出和吸收，并测定了LPZ在大鼠和犬体内的BA。作为表面活性剂，使用吐温80、聚氧60氢化蓖麻油衍生物（HC 0 -60）和PEG-8辛酸/癸酸甘油酯（Labrasol）。作为吸附剂，使用多孔二氧化硅（Sylysia 550，320）、硅酸镁铝（Neusilin S-2，NS 2N，US 2）和多孔硅酸钙（Florite RE）。小肠给予5.0 mg/kg LPZ后，含HCO-60的溶液显示最高血浆LPZ浓度-时间曲线，其C-max和AUC分别为0.46 +/- 0.01 mug/mL和0.73 +/- 0.03 mug h/mL。与静脉注射2.0mg/kg的LPZ溶液相比，HCO-60溶液中的LPZ的BA为39.0%，约为LPZ粉末的7倍。为了用HCO-60固化LPZ溶液，使用吸附剂，并将所得固体制剂用于体外释放实验。Sylysia 320、Neusilin S-2和Neusilin NS 2的T50%约为1 h。为了评价这些固体制剂的BA，在大鼠中进行吸收研究。Sylysia 550系统显示出比其他系统更高的AUC，显示出28.1%的BA。将Sylysia 550系统装入肠溶胶囊中，经口给予犬，并将BA与肠溶片进行比较。Sylysia 550系统的AUC为2.16 +/- 0.26 μ g h/mL，大于肠溶片，BA为71.7%。由LPZ、表面活性剂和吸附剂组成的固体体系是提高LPZ吸附能力的有效手段。(C)2004 Elsevier B. V.保留所有权利。
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 S-2, 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 mug/mL and 0.73 +/- 0.03 mug h/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 S-2 and Neusilin NS2 showed the T50% of about 1 h. 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. The AUC of Sylysia 550 system was 2.16 +/- 0.26 mug h/mL and was greater than enteric tablet and the BA of 71.7% was obtained. Solid system composed of LPZ, surfactant and adsorbent has suggested the possibility as a good tool to improve the BA of LPZ. (C) 2004 Elsevier B.V. All rights reserved.