Quality by Design approach to spray drying processing of crystalline nanosuspensions

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• 作者：Sumit Kumar^a ; Rajeev Gokhale^b ; Diane J. Burgess^a ; ^{diane.burgess@uconn.edu" class="auth_mail}
• 关键词：ANOVA ; analysis of variance ; API ; active pharmaceutical ingredient ; BCS ; biopharmaceutical classification system ; CCD ; central cubic design ; CQA ; critical quality attributes ; Cmax ; maximum drug concentration ; Ct Pt ; center point ; DoE ; Design of Experiment ; DSC ; differential scanning calorimeter ; PXRD ; powder X-ray diffraction ; QbD ; Quality by Design ; Tg ; glass transition temperature ; Tmax ; time to reach maximum concentration ; Tm ; melting temperature
• 刊名：International Journal of Pharmaceutics
• 出版年：10 April, 2014
• 年：2014
• 卷：464
• 期：1-2
• 页码：234-242
• 全文大小：2150 K

文摘

Quality by Design (QbD) principles were explored to understand spray drying process for the conversion of liquid nanosuspensions into solid nano-crystalline dry powders using indomethacin as a model drug. The effects of critical process variables: inlet temperature, flow and aspiration rates on critical quality attributes (CQAs): particle size, moisture content, percent yield and crystallinity were investigated employing a full factorial design. A central cubic design was employed to generate the response surface for particle size and percent yield. Multiple linear regression analysis and ANOVA were employed to identify and estimate the effect of critical parameters, establish their relationship with CQAs, create design space and model the spray drying process. Inlet temperature was identified as the only significant factor (p value <0.05) to affect dry powder particle size. Higher inlet temperatures caused drug surface melting and hence aggregation of the dried nano-crystalline powders. Aspiration and flow rates were identified as significant factors affecting yield (p value <0.05). Higher yields were obtained at higher aspiration and lower flow rates. All formulations had less than 3% (w/w) moisture content. Formulations dried at higher inlet temperatures had lower moisture compared to those dried at lower inlet temperatures.