Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, Alexandria 21521, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, Alexandria 21521, Egypt.
Eur J Pharm Sci. 2014 Jul 16;58:44-54. doi: 10.1016/j.ejps.2014.03.004. Epub 2014 Apr 2.
Emulsion electrospinning is a multifactorial process used to generate nanofibers loaded with hydrophilic drugs or macromolecules for diverse biomedical applications. Emulsion electrospinnability is greatly impacted by the emulsion pharmaceutical attributes. The aim of this study was to apply a quality by design (QbD) approach based on design of experiments as a risk-based proactive approach to achieve predictable critical quality attributes (CQAs) in w/o emulsions for electrospinning. Polycaprolactone (PCL)-thickened w/o emulsions containing doxycycline HCl were formulated using a Span 60/sodium lauryl sulfate (SLS) emulsifier blend. The identified emulsion CQAs (stability, viscosity and conductivity) were linked with electrospinnability using a 3(3) factorial design to optimize emulsion composition for phase stability and a D-optimal design to optimize stable emulsions for viscosity and conductivity after shifting the design space. The three independent variables, emulsifier blend composition, organic:aqueous phase ratio and polymer concentration, had a significant effect (p<0.05) on emulsion CQAs, the emulsifier blend composition exerting prominent main and interaction effects. Scanning electron microscopy (SEM) of emulsion-electrospun NFs and desirability functions allowed modeling of emulsion CQAs to predict electrospinnable formulations. A QbD approach successfully built quality in electrospinnable emulsions, allowing development of hydrophilic drug-loaded nanofibers with desired morphological characteristics.
乳液静电纺丝是一种多因素过程，用于生成负载亲水性药物或大分子的纳米纤维，用于多种生物医学应用。乳液的可静电纺丝性受乳液药物属性的极大影响。本研究的目的是应用基于设计的质量（QbD）方法，基于实验设计作为一种基于风险的主动方法，以实现 w/o 乳液中用于静电纺丝的可预测关键质量属性（CQAs）。使用 Span 60/十二烷基硫酸钠（SLS）乳化剂混合物配制载有盐酸多西环素的聚己内酯（PCL）增稠 w/o 乳液。使用 3(3)因子设计将确定的乳液 CQAs（稳定性、粘度和电导率）与可纺性联系起来，以优化乳液组成以实现相稳定性，并用 D-最优设计优化稳定乳液的粘度和电导率，以转移设计空间。三个独立变量，乳化剂混合物组成、有机相：水相比例和聚合物浓度，对乳液 CQAs 有显著影响（p<0.05），乳化剂混合物组成具有显著的主效应和相互作用效应。乳液电纺纳米纤维的扫描电子显微镜（SEM）和理想函数允许对乳液 CQAs 进行建模，以预测可静电纺丝的配方。QbD 方法成功地在可静电纺丝乳液中建立了质量，允许开发具有所需形态特征的亲水性药物负载纳米纤维。
