Shah Dhaval A, Murdande Sharad B, Dave Rutesh H
J Pharm Sci. 2016 Jan;105(1):10-24. doi: 10.1002/jps.24694. Epub 2016 Jan 13.
Nanocrystals have emerged as a potential formulation strategy to eliminate the bioavailability-related problems by enhancing the initial dissolution rate and moderately super-saturating the thermodynamic solubility. This review contains an in-depth knowledge of, the processing method for formulation, an accurate quantitative assessment of the solubility and dissolution rates and their correlation to observe pharmacokinetic data. Poor aqueous solubility is considered the major hurdle in the development of pharmaceutical compounds. Because of a lack of understanding with regard to the change in the thermodynamic and kinetic properties (i.e., solubility and dissolution rate) upon nanosizing, we critically reviewed the literatures for solubility determination to understand the significance and accuracy of the implemented analytical method. In the latter part, we reviewed reports that have quantitatively studied the effect of the particle size and the surface area change on the initial dissolution rate enhancement using alternative approaches besides the sink condition dissolution. The lack of an apparent relationship between the dissolution rate enhancement and the observed bioavailability are discussed by reviewing the reported in vivo data on animal models along with the particle size and food effect. The review will provide comprehensive information to the pharmaceutical scientist in the area of nanoparticulate drug delivery.
纳米晶体已成为一种潜在的制剂策略，通过提高初始溶解速率和适度超饱和热力学溶解度来消除与生物利用度相关的问题。本综述包含了对制剂加工方法的深入了解、对溶解度和溶解速率的准确定量评估及其与观察到的药代动力学数据的相关性。水溶性差被认为是药物化合物开发中的主要障碍。由于对纳米尺寸下热力学和动力学性质（即溶解度和溶解速率）变化缺乏了解，我们对溶解度测定的文献进行了批判性回顾，以了解所采用分析方法的意义和准确性。在后者部分，我们回顾了除漏槽条件溶解外，使用替代方法定量研究粒径和表面积变化对初始溶解速率增强影响的报告。通过回顾动物模型上报道的体内数据以及粒径和食物效应，讨论了溶解速率增强与观察到的生物利用度之间缺乏明显关系的问题。本综述将为纳米颗粒药物递送领域的药物科学家提供全面信息。
