Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA.
Mol Pharm. 2010 Oct 4;7(5):1858-70. doi: 10.1021/mp100209b. Epub 2010 Sep 16.
In this manuscript, the determination of solubility of crystalline drug nanosuspensions by a range of methods is critically investigated. As the determinations of solubility were performed in the presence of the solubilizing nanosuspension stabilizer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), the potential effects of this excipient on the measurements were studied first. Solubility data of nanosuspensions of itraconazole, loviride, phenytoin and naproxen were generated using different methodologies. Data obtained using separation-based methodologies (centrifugation, filtration and ultracentrifugation) proved to be of limited use, due to poor nanoparticle separation efficiencies and/or significant adsorption of TPGS onto the nanoparticle surfaces. Light scattering and turbidity were found to be more suitable for the determination of nanosuspension solubility. The obtained data show that, unlike earlier reports, the solubility increases due to nanosizing are small, with measured increases of only 15%. These solubility increases are in fair agreement with what would be predicted based on the Ostwald-Freundlich equation.
本文批判性地研究了通过一系列方法来确定结晶药物纳米悬浮液的溶解度。由于在溶解纳米悬浮稳定剂 d-α-生育酚聚乙二醇 1000 琥珀酸酯（TPGS）的存在下进行了溶解度的测定，因此首先研究了该赋形剂对测量的潜在影响。使用不同的方法学生成了伊曲康唑、洛匹那韦、苯妥英和萘普生纳米悬浮液的溶解度数据。基于分离的方法学（离心、过滤和超速离心）获得的数据由于纳米颗粒分离效率差和/或 TPGS 对纳米颗粒表面的显著吸附而证明用途有限。光散射和浊度被发现更适合于纳米悬浮液溶解度的测定。所得数据表明，与早期报告不同，由于纳米化导致的溶解度增加很小，仅测量增加了 15%。这些溶解度的增加与根据奥斯特瓦尔德-弗伦德里希方程预测的结果相当一致。
