Tuomela Annika, Hirvonen Jouni, Peltonen Leena
Division of Pharmaceutical Chemistry and Technology, P.O. Box 56 (Viikinkaari 5 E), University of Helsinki, 00014 Helsinki, Finland.
Pharmaceutics. 2016 May 20;8(2):16. doi: 10.3390/pharmaceutics8020016.
Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure-a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer's role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro-in vivo correlation with nanocrystalline products, and stabilizers' effect on higher bioavailability are discussed.
药物纳米晶体是用于药物递送目的的一种通用选择，并且随着难溶性药物材料的数量一直在增加，该领域开展了更多研究。药物纳米晶体具有简单的结构——固体药物核心被一层稳定剂包围。然而，尽管结构相当简单，但为特定药物选择合适的稳定剂可能具有挑战性。大多数情况下，稳定剂的选择纯粹基于物理稳定性的要求，例如在药物纳米晶体形成后尽可能长时间地保持纳米尺寸的粒径。然而，还值得考虑的是，稳定剂可通过与细胞和细胞层的相互作用影响最终制剂中的生物利用度。此外，纳米晶体的形成只是一个工艺步骤，对于最终制剂，通常会在组合物中添加更多辅料。稳定剂在最终制剂中的作用可能不止于稳定纳米晶体的粒径。一个很好的例子是稳定剂在冷冻干燥过程中作为冷冻保护剂的作用。在本综述中，讨论了稳定剂的稳定作用、其在最终纳米晶体制剂中的作用、纳米晶产品实现体外-体内相关性面临的挑战以及稳定剂对提高生物利用度的影响。
