Research Pharmaceutics and Drug Product Development, Merck Serono, Frankfurter Str. 250, 64293, Darmstadt, Germany.
Pharm Res. 2012 Oct;29(10):2887-901. doi: 10.1007/s11095-012-0795-4. Epub 2012 Jun 12.
Nanocrystals exhibit enhanced dissolution rates and can effectively increase the bioavailability of poorly water soluble drug substances. However, methods for in vitro characterization of dissolution are unavailable. The objective of this study was to develop an in situ noninvasive analytical method to measure dissolution of crystalline nanosuspensions based on light scattering.
Fenofibrate nanosuspensions were prepared by wet media milling. Their solubilities and dissolution profiles in simulated gastric fluid supplemented with 0.1% Tween(®) 80 were measured in a small scale setup with an instrument for dynamic light scattering and the intensity of scattered light as readout parameter.
A good correlation was achieved between the dissolution profile of a nanosuspension measured in the light scattering setup and a conventional dissolution experiment. Nanosuspensions of 120-270 nm size could be distinguished by the light scattering method. The suspensions dissolved within 1.9-12.3 min. Over a concentration range of 40-87% of the solubility dissolution profiles of a nanosuspension with 140 nm were monitored and the determined total dissolution times were in good agreement with the Noyes-Whitney dissolution model.
A noninvasive, sensitive and reproducible method is presented to assess nanocrystal dissolution. In situ measurements based on light scattering allow a straightforward experimental setup with high temporal resolution.
纳米晶体表现出增强的溶解速率，并且可以有效地提高水溶性差的药物物质的生物利用度。然而，目前缺乏用于体外溶解特性表征的方法。本研究的目的是开发一种基于光散射的用于测量结晶纳米混悬剂溶解的原位非侵入性分析方法。
通过湿介质研磨制备非诺贝特纳米混悬剂。在配备动态光散射仪器的小型设备中，使用含有 0.1%吐温 80 的模拟胃液，测量其在模拟胃液中的溶解度和溶解曲线。以散射光强度作为读出参数。
光散射装置中测量的纳米混悬剂的溶解曲线与常规溶解实验之间具有良好的相关性。光散射方法可区分 120-270nm 大小的纳米混悬剂。混悬剂在 1.9-12.3 分钟内溶解。在 40-87%溶解度范围内监测了粒径为 140nm 的纳米混悬剂的溶解曲线，并且确定的总溶解时间与 Noyes-Whitney 溶解模型吻合良好。
本研究提出了一种用于评估纳米晶体溶解的非侵入性、灵敏且重现性好的方法。基于光散射的原位测量方法具有简单的实验设置和高时间分辨率。
