Institute of Pharmaceutical Technology, Goethe University, Frankfurt, Germany.
J Pharm Pharmacol. 2012 Jul;64(7):931-43. doi: 10.1111/j.2042-7158.2012.01520.x. Epub 2012 May 2.
This mini-review describes the theoretical advantages of nanosizing drugs in terms of dissolution and the characterization of their behaviour with in-vitro dissolution testing.
It is shown that the increase in dissolution rate is not commensurate with common theories. The calculation of dissolution rate by surface area increase using the Nernst-Brunner equation is inappropriate since the diffusion layer, δ, cannot be assessed. These results highlight the importance of an appropriate experimental design to assess the dissolution rate in vitro, which will then serve as a building block for establishing in vitro-in vivo correlations. Several techniques to assess the amount of released drug in dissolution testing are discussed, some through a review of current literature (dialysis, turbidity measurement methods, fibre optics, asymmetrical flow-field-flow fractionation), some through experimental experience (ion-selective electrode and syringe filters). Further methods, such as microdialysis, ultrasonic resonance technology and centrifugal filter devices, are reviewed from literature with some additional data obtained in house. The techniques are further discussed with a view to coupling the results with simulation software tools such as STELLA© to predict the in-vivo behaviour of the drug. In doing so, it is necessary to generate experimental data on the dissolution rate, since this cannot be calculated directly from the surface increase of drug particles but rather depends on further factors such as the boundary layer thickness.
It was concluded that syringe filters of appropriate pore size and the ion-selective electrode appear to be suitable for measurement of the dissolution rate of nanosized drugs.
本综述性微型研究描述了纳米药物在溶解方面的理论优势，并介绍了采用体外溶解试验对其行为进行特征描述的方法。
结果表明，溶解速率的增加与常见理论并不相符。采用 Nernst-Brunner 方程通过表面积增加来计算溶解速率是不恰当的，因为无法评估扩散层 δ。这些结果突出表明，评估体外溶解速率时，需要进行适当的实验设计，这将作为建立体外-体内相关性的基础。本文讨论了几种评估溶解试验中药物释放量的技术，其中一些是通过对当前文献的回顾（透析、浊度测量方法、光纤、非对称流场-流分离），另一些是通过实验经验（离子选择性电极和注射器过滤器）获得的。本文还从文献中综述了其他方法，如微透析、超声共振技术和离心过滤装置，并在实验室中获得了一些额外的数据。进一步讨论了这些技术，以期将结果与 STELLA©等模拟软件工具相结合，预测药物的体内行为。在这样做的过程中，有必要生成关于溶解速率的实验数据，因为这不能直接从药物颗粒的表面积增加来计算，而是取决于边界层厚度等其他因素。
研究结果表明，合适孔径的注射器过滤器和离子选择性电极似乎适合测量纳米药物的溶解速率。
