In vivo assessment of oral administration of probucol nanoparticles in rats ラット経口投与におけるナノ微粒子化プロブコールの評価

博士論文

研究科: 千葉大学大学院薬学研究院

修了年:2008

学位:千大院医薬博甲第薬67号

Pharmacokinetic profiles of probucol were evaluated after oral administration of the various nano-suspensions 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 distilled water were 28, 75 and 89 nm, respectively, compared to the unprocessed probucol was 27 μm. The ternary GM suspensions with PVP K17/SDS and PVP K30/SDS were stable at 25 °C. However the particle size of probucol from the ternary GM with PVP K12/SDS gradually increased was attributable to insufficient surface coverage of the nanoparticles with PVP K12-SDS micelle complex. 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.