In vivo assessment of oral administration of probucol nanoparticles in rats
In vivo assessment of oral administration of probucol nanoparticles in rats
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DOI：
10.1248/bpb.31.321
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发表时间：
2008-02-01
影响因子：
2
通讯作者：
Yamamoto, Keiji
中科院分区：
文献类型：
--
作者：
Shudo, Jyutaro;Pongpeerapat, Adchara;Yamamoto, Keiji
在大鼠中口服各种纳米混悬剂后评价普罗布考的药代动力学特征。通过与不同分子量的聚乙烯吡咯烷酮（PVP K12、PVP K17和PVP K30）和十二烷基硫酸钠（SDS）共研磨制备普罗布考纳米粒。将三元研磨混合物（GM）、普罗布考/PVP K12/SDS、普罗布考/PVP K17/SDS和普罗布考/PVP K30/SDS分散到水中后，普罗布考的平均粒径分别为28、75和89 μ m。含有PVP K17/SDS和PVP K30/SDS的三元GM悬浮液在25 ℃下稳定。而PVP K12/SDS三元GM的普罗布考粒径逐渐增大。普罗布考的药代动力学曲线表明，除了粒径外，PVP和SDS覆盖的颗粒表面条件的变化影响普罗布考体内吸收的改善。与PVP K17/SDS和PVP K30/SDS的GM相比，PVP K12/SDS的三元GM表现出上级普罗布考吸收的改善。与未处理的普罗布考相比，含有PVP或SDS的二元GM和含有PVP和/或SDS的物理混合物在血浆浓度-时间曲线下面积方面没有显示出显著差异。结论：PVP K12和SDS共研磨法制备普罗布考纳米粒是一种很有前途的提高生物利用度的方法。
Pharmacokinetic profiles of probucol were evaluated after oral administration of the various nanosuspensions in rats. Probucol nanoparticles were prepared by co-grinding with various molecular weights of polyvinylpyrrolidone (PVP K12, PVP K17 and PVP K30) and sodium dodecyl sulfate (SDS). The average particle sizes of probucol after dispersing the ternary ground mixtures (GMs), probucol/PVP K12/SDS, probucol/PVP K17/SDS and probucol/PVP K30/SDS into water were 28, 75 and 89 urn respectively. The ternary GM suspensions with PVP K17/SDS and PVP K30/SDS were stable at 25 degrees C. However the particle size of probucol from the ternary GM with PVP K12/SDS gradually increased. Pharmacokinetic profiles of probucol indicated that variation in particle surface condition covered with PVP and SDS in addition to the particle size affected the improvement of in vivo absorption of probucol. The ternary GM with PVP K12/SDS exhibited a superior improvement of probucol absorption compared to the GMs with PVP K17/SDS and PVP K30/SDS. The binary GM with PVP or SDS and physical mixtures with PVP and/or SDS did not show significant differences in the area under the plasma concentration-time curve compared to the unprocessed probucol. In conclusion, preparation of probucol nanoparticles by co-grinding with PVP K12 and SDS could be a promising method for bioavailability enhancement.