Abstract：
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.
摘要：
这项研究采用了质量设计（QbD）方法来喷雾干燥由Soluplus®和微晶纤维素组成的无定形克霉唑纳米悬浮液（CLT-NS）。使用Box-Behnken设计，进行了系统的评估，以分析进口温度的影响，%抽吸,和进料速率对克霉唑喷雾干燥纳米悬浮液（CLT-SDNS）的关键质量属性（CQA）的影响。在这项研究中,采用回归分析和方差分析来检测显著因素和相互作用，能够开发喷雾干燥过程的预测模型。优化后,CLT-SD-NS使用X射线粉末衍射(XRPD)进行分析，傅里叶变换红外光谱(FTIR),动态扫描量热法(DSC),和体外溶出研究。结果显示了显著的变量，包括入口温度,进料速率,和吸入率，影响产量，再分散性指数（RDI），和最终产品的水分含量。为关键质量属性（CQA）创建的模型显示出统计学意义，p值为0.05。XRPD和DSC证实了CLT-SD-NS中CLT的非晶态，和FTIR表明CLT和赋形剂之间没有相互作用。在体外溶解研究中显示，CLT-SD-NS的溶解速率提高（在DI水中增加3.12倍，在pH7.2溶解介质下增加5.88倍），归于环状再分散纳米无定形CLT颗粒。利用实验设计（DoE）方法进行精心设计的研究。
