Shah Dhaval A, Patel Manan, Murdande Sharad B, Dave Rutesh H
a Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University , Brooklyn , NY , USA ;
b Drug Product Design , Pfizer Worldwide R&D , Groton , CT , USA.
Drug Dev Ind Pharm. 2016 Nov;42(11):1842-50. doi: 10.1080/03639045.2016.1178770. Epub 2016 May 4.
The purpose for the current research is to compare and evaluate physiochemical properties of spray-dried (SD) microcrystals (MCs), nanocrystals (NCs), and nanocrystals with a dispersion agent (NCm) from a poorly soluble compound. The characterization was carried out by performing size and surface analysis, interfacial tension (at particle moisture interface), and in-vitro drug dissolution rate experiments. Nanosuspensions were prepared by media milling and were spray-dried. The SD powders that were obtained were characterized morphologically using scanning electron microscopy (SEM), polarized light microscopy (PLM), and Flowchem. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier transfer infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) for the identification of the crystalline nature of all the SD powders. The powders were characterized for their redispersion tendency in the water and in pH 1.2. Significant differences in redispersion were noted for both the NCs in both dissolution media. The interfacial tension for particle moisture interface was determined by applying the BET (Braunauer-Emmett-Teller) equation to the vapor sorption data. No significant reduction in the interfacial tension was observed between MCs and NCs; however, a significant reduction in the interfacial tension was observed for NCm at both 25 °C and 35 °C temperatures. The difference in interfacial tension and redispersion behavior can be attributed to a difference in the wetting tendency for all the SD powders. The dissolution studies were carried out under sink and under non-sink conditions. The non-sink dissolution approach was found suitable for quantification of the dissolution rate enhancement, and also for providing the rank order to the SD formulations.
当前研究的目的是比较和评估喷雾干燥（SD）微晶（MCs）、纳米晶体（NCs）以及添加分散剂的纳米晶体（NCm）（均由难溶性化合物制成）的物理化学性质。通过进行粒度和表面分析、界面张力（在颗粒 - 水分界面处）以及体外药物溶出速率实验来进行表征。通过介质研磨制备纳米混悬液并进行喷雾干燥。使用扫描电子显微镜（SEM）、偏光显微镜（PLM）和Flowchem对获得的SD粉末进行形态表征。使用X射线粉末衍射（XRPD）、傅里叶变换红外光谱（FT - IR）和差示扫描量热法（DSC）进行固态表征，以确定所有SD粉末的晶型性质。对这些粉末在水和pH 1.2条件下的再分散倾向进行了表征。在两种溶出介质中，NCs的再分散均存在显著差异。通过将BET（布鲁瑙尔 - 埃米特 - 特勒）方程应用于蒸汽吸附数据来测定颗粒 - 水分界面的界面张力。MCs和NCs之间未观察到界面张力有显著降低；然而，在25°C和35°C温度下，NCm的界面张力均有显著降低。界面张力和再分散行为的差异可归因于所有SD粉末的润湿倾向不同。溶出研究在漏槽和非漏槽条件下进行。发现非漏槽溶出方法适用于定量溶出速率的提高，也适用于对SD制剂进行排序。
