Understanding Critical Quality Attributes for Nanocrystals from Preparation to Delivery

Molecules

Leena Peltonen¹  Clare Strachan¹  Thomas Rades²  Holger Grohganz² 

[1] Division of Pharmaceutical Chemistry and Technology, University of Helsinki, P. O. Box 56, Viikinkaari 5 E, 00014, Finland

关键词: bioavailability;    drug nanocrystals;    permeation;    precipitation;    solubility;    stability;    supersaturation;   

DOI  :  10.3390/molecules201219851

来源: mdpi

【 摘 要 】

Poor solubility of active pharmaceutical ingredients (APIs) is a great challenge for the pharmaceutical industry and, hence, drug nanocrystals are widely studied as one solution to overcome these solubility problems. Drug nanocrystals have comparatively simple structures which make them attractive for the formulation for poorly soluble drugs, and their capability to improve the dissolution in vitro is easily demonstrated, but turning the in vitro superior properties of nanocrystals to success in vivo, is often demanding: controlled (including enhanced) drug dissolution followed by successful permeation is not guaranteed, if for example, the dissolved drug precipitates before it is absorbed. In this review critical quality attributes related to nanocrystal formulations from production to final product performance in vivo are considered. Many important parameters exist, but here physical stability (aggregation tendency and solid state form), solubility properties influencing dissolution and supersaturation, excipient use to promote the maintenance of supersaturation, and finally the fate of nanocrystals in vivo are the main subjects of our focus.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.