Holm René, Andresen Lene, Strange Claus
Preformulaton, H.Lundbeck A/S, Ottilavej 9, Valby 2500, Denmark.
Pharmaceutical Development, H.Lundbeck A/S, Ottilavej 9, Valby 2500, Denmark.
Results Pharma Sci. 2011 Oct 8;1(1):57-9. doi: 10.1016/j.rinphs.2011.09.001. eCollection 2011 May.
Oral administration of Lu 35-138, a low aqueous soluble compound, was investigated in three different formulations containing sulfobutylether β-cyclodextrin (SBE7βCD) in fasted beagle dogs. The evaluated formulations was (i) a SBE7βCD solution, (ii) a spray dried solution filled into hard gelatine capsules, and (iii) a direct compressible tablet containing SBE7βCD. The three formulations did not lead any significant differences in the obtained AUCs, though a trend was observed for the highest absorption when Lu 35-138 was dosed in the cyclodextrin solution. These results demonstrate that a solid formulation with a relative low content of cyclodextrins can be used to increase the bioavailability of a low water soluble compound to a relative high level when compared to a cyclodextrin solution.
在禁食的比格犬中，对低水溶性化合物Lu 35-138的三种不同制剂进行了口服给药研究，这三种制剂均含有磺丁基醚β-环糊精（SBE7βCD）。所评估的制剂为：（i）SBE7βCD溶液；（ii）填充于硬明胶胶囊中的喷雾干燥溶液；（iii）含有SBE7βCD的直接压片。尽管当Lu 35-138以环糊精溶液给药时观察到最高吸收趋势，但三种制剂的AUCs无显著差异。这些结果表明，与环糊精溶液相比，含有相对低含量环糊精的固体制剂可用于将低水溶性化合物的生物利用度提高到相对较高水平。
