Nanocrystal formulation is a well-established approach for improving oral absorption of poorly water-soluble drugs. However, it is difficult to predict the in vivo performance of nanocrystal formulations from in vitro dissolution studies. The object of the present study was to investigate the in vitro-in vivo correlation of nanocrystal formulations of different particle sizes. A microsuspension and three nanosuspensions with different particle sizes for model drugs, fenofibrate and megestrol acetate, were prepared. In the comparison between the microsuspension and the nanosuspension having the smallest particle sizes, drug permeation rates from the nanosuspension were about 3-fold higher in the dissolution-permeation study. On the other hand, the solubility enhancement effect due to nanocrystal formation was only up by 1.4-fold, suggesting that nanocrystal formulations dramatically improved not the solubility but the apparent permeability. The oral absorption rate in rats increased with particle size reduction. There were positive and very strong correlations (R2 > 0.95) between the in vitro permeation rate and in vivo maximum absorption rate. We concluded that the enhanced permeability rate due to nanocrystal formation is the main factor for improving oral absorption, and the in vitro dissolution-permeation study could be useful for predicting oral absorption enhancement of nanocrystal formulations.

中文翻译：

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纳米晶体制剂口服吸收增强的关键因素的阐明：纳米晶体的体外-体内相关性。

纳米晶体制剂是改善水溶性差的药物的口服吸收的公认方法。然而，难以通过体外溶出研究来预测纳米晶体制剂的体内性能。本研究的目的是研究不同粒径的纳米晶体制剂的体外-体内相关性。制备了用于模型药物非诺贝特和醋酸孕甾酮的微悬浮液和三种不同粒径的纳米悬浮液。在具有最小粒径的微悬浮液和纳米悬浮液之间的比较中，在溶解渗透研究中，来自纳米悬浮液的药物渗透速率高约3倍。另一方面，由于形成纳米晶体而增加的溶解度仅提高了1.4倍，这表明纳米晶体配方不仅可以显着提高溶解度，而且还可以显着提高表观渗透性。随着颗粒尺寸的减小，大鼠的口服吸收率增加。体外渗透率与体内最大吸收率之间存在正相关且非常强的相关性（R2> 0.95）。我们得出的结论是，由于纳米晶体的形成而增加的渗透率是改善口服吸收的主要因素，而体外溶出-渗透研究对于预测纳米晶体制剂的口服吸收增强可能是有用的。95）在体外渗透率和体内最大吸收率之间。我们得出的结论是，由于纳米晶体的形成而增加的渗透率是改善口服吸收的主要因素，而体外溶出-渗透研究对于预测纳米晶体制剂的口服吸收增强可能是有用的。95）在体外渗透率和体内最大吸收率之间。我们得出的结论是，由于纳米晶体的形成而增加的渗透率是改善口服吸收的主要因素，而体外溶出-渗透研究对于预测纳米晶体制剂的口服吸收增强可能是有用的。