Department of Pharmacy, The First Affiliated Hospital of General Hospital of PLA, No. 51 Fucheng Road, Beijing, 100048, China.
Pharm Res. 2013 Feb;30(2):307-24. doi: 10.1007/s11095-012-0889-z. Epub 2012 Oct 17.
The limited solubility and dissolution rate exhibited by poorly soluble drugs is major challenges in the pharmaceutical process. Following oral administration, the poorly soluble drugs generally show a low and erratic bioavailability which may lead to therapeutic failure. Pure drug nanocrystals, generated by "bottom up" or "top down" technologies, facilitate a significant improvement on dissolution behavior of poorly soluble drugs due to their enormous surface area, which in turn lead to substantial improvement in oral absorption. This is the most distinguished achievement of drug nanocrystals among their performances in various administration routes, reflected by the fact that most of the marketed products based on the nanocrystals technology are for oral application. After detailed investigations on various technologies associated with production of drug nanocrystals and their in vitro physicochemical properties, during the last decade more attentions have been paid into their in vivo behaviors. This review mainly describes the in vivo performances of oral drug nanocrystals exhibited in animals related to the pharmacokinetic, efficacy and safety characteristics. The technologies and evaluation associated with the solidification process of the drug nanocrystals suspensions were also discussed in detail.
难溶性药物的溶解度和溶解速率有限，这是药物制剂过程中的主要挑战。口服给药后，难溶性药物通常表现出低而不稳定的生物利用度，这可能导致治疗失败。通过“自上而下”或“自下而上”技术生成的纯药物纳米晶体由于其巨大的表面积，极大地改善了难溶性药物的溶解行为，从而显著提高了口服吸收。这是药物纳米晶体在各种给药途径中的性能中最显著的成就，这反映在大多数基于纳米晶体技术的上市产品都是用于口服应用。在详细研究了与药物纳米晶体生产及其体外物理化学性质相关的各种技术之后，在过去十年中，人们更加关注它们的体内行为。本文主要描述了动物体内与药代动力学、疗效和安全性特征相关的口服药物纳米晶体的体内性能。还详细讨论了与药物纳米晶体混悬液固化过程相关的技术和评价。
