Shudo Jyutaro, Pongpeerapat Adchara, Wanawongthai Chalermphon, Moribe Kunikazu, Yamamoto Keiji
Graduate School of Pharmaceutical Sciences, Chiba University, Inage-ku, Chiba, Japan.
Biol Pharm Bull. 2008 Feb;31(2):321-5. doi: 10.1248/bpb.31.321.
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 nm 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.
在大鼠口服各种纳米混悬液后评估了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）以及十二烷基硫酸钠（SDS）共同研磨制备了普罗布考纳米颗粒。将三元研磨混合物（GMs），即普罗布考/PVP K12/SDS、普罗布考/PVP K17/SDS和普罗布考/PVP K30/SDS分散于水中后，普罗布考的平均粒径分别为28、75和89 nm。含有PVP K17/SDS和PVP K30/SDS的三元GM混悬液在25℃下稳定。然而，含有PVP K12/SDS的三元GM中普罗布考的粒径逐渐增大。普罗布考的药代动力学特征表明，除粒径外，覆盖有PVP和SDS的颗粒表面状况的变化影响了普罗布考体内吸收的改善。与含有PVP K17/SDS和PVP K30/SDS的GMs相比，含有PVP K12/SDS的三元GM对普罗布考吸收的改善更显著。与未处理的普罗布考相比，含有PVP或SDS的二元GM以及与PVP和/或SDS的物理混合物在血浆浓度-时间曲线下面积方面未显示出显著差异。总之，通过与PVP K12和SDS共同研磨制备普罗布考纳米颗粒可能是一种提高生物利用度的有前景的方法。
