Division of Pharmaceutics Sciences, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, The Long Island University, Brooklyn, NY, 11201, USA.
Experic, LLC, Cranbury, NJ, USA.
AAPS PharmSciTech. 2024 Jul 13;25(6):164. doi: 10.1208/s12249-024-02871-1.
This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.
本研究采用质量源于设计（QbD）方法制备包含 Soluplus 和微晶纤维素的无定形克霉唑纳米混悬剂（CLT-NS）。采用 Box-Behnken 设计，对入口温度、%吸入率和进料速率对克霉唑喷雾干燥纳米混悬剂（CLT-SDNS）的关键质量属性（CQAs）的影响进行了系统评估。在本研究中，回归分析和方差分析用于检测显著因素和相互作用，从而开发喷雾干燥过程的预测模型。经过优化后，CLT-SD-NS 进行 X 射线粉末衍射（XRPD）、傅里叶变换红外光谱（FTIR）、动态扫描量热法（DSC）和体外溶解研究分析。结果表明，入口温度、进料速率和吸入速率等显著变量影响最终产品的收率、再分散指数（RDI）和水分含量。关键质量属性（CQAs）的模型显示在 p 值为 0.05 时具有统计学意义。XRPD 和 DSC 证实 CLT 在 CLT-SD-NS 中处于无定形态，FTIR 表明 CLT 与赋形剂之间没有相互作用。体外溶解研究表明 CLT-SD-NS 的溶解速率得到改善（在 DI 水中增加 3.12 倍，在 pH 7.2 溶解介质中增加 5.88 倍），这归因于快速再分散的纳米级无定形 CLT 颗粒。该研究采用实验设计（DoE）方法进行了精心设计。
