Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s)
Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s)
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DOI：
10.1016/j.ijpharm.2016.12.010
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发表时间：
2017-01-30
影响因子：
5.8
通讯作者：
Katare, O. P.
中科院分区：
文献类型：
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作者：
Garg, Neeraj K.;Sharma, Gajanand;Katare, O. P.
本研究旨在采用质量设计（QbD）为导向的方法制备和表征负载乙酰氯芬酸的纳米结构脂质载体（nlc）。评估了NLCs的透皮渗透潜力和稳定性。采用质量设计（Quality by Design, QbD）方法制备并表征了乙酰氯芬酸负载的纳米结构脂质载体（nlc），并进一步评价了其透皮渗透潜力和稳定性。选择不同的脂质和表面活性剂作为临界材料属性（cma），采用微乳液法制备NLCs。采用3(3)因子设计对NLCs进行优化，并对不同的关键质量属性（cqa），即粒径、多分散性指数（PDI）、zeta电位、体外药物释放、包封效率进行评价。系统评价脂质、油脂比、表面活性剂浓度等CMAs对cqa（即药物包封效率和粒径）的影响，以优化nclc。将优化后的NLCs进一步掺入carbopol凝胶中，对其进行结构和流变学表征，并进行体外和体内评价。优化后的ACE-NLCs为球形纳米级，具有较高的载药量和包封效率。体外释药实验结果表明，所制制剂符合Korsmeyer-Peppas模型，呈菲克扩散。释放为双相释放，即最初的爆发释放，随后持续释放长达48小时。优化的nlc凝胶配方具有优异的质地、流变学特征，对角化过度细胞（HaCaT细胞系）具有更好的细胞摄取效率，与市场上销售的配方相比，具有更高的体外皮肤渗透效率。总之，对卡拉胶诱导水肿小鼠的皮肤动力学建模和药效学研究表明，乙酰氯芬酸负载的NLCs水凝胶可能是一种更好的针对不同皮肤层的递送替代方案。(C) 2016 Elsevier B.V.版权所有
Present study was designed to prepare and characterize aceclofenac loaded nanostructured lipid carriers (NLCs) employing Quality by Design (QbD)-oriented approach. The NLCs were evaluated for their transdermal penetration potential and stability. Aceclofenac loaded nanostructured lipid carriers (NLCs) were prepared & characterized, by employing Quality by Design (QbD)-oriented approach and further evaluated for transdermal penetration potential and stability. Different lipids and surfactants were chosen to prepare NLCs using microemulsion method as critical material attributes (CMAs). A 3(3) factorial design was used for optimization of NLCs, and evaluating them for different critical quality attributes (CQAs), viz. particle size, polydispersity index (PDI), zeta potential, in vitro drug release, entrapment efficiency. The effect of CMAs such as lipids, oil: lipid ratio and concentration of surfactants on CQAs viz. drug entrapment efficiency and particle size were systematically evaluated to optimize NLCs. The optimized NLCs were further incorporated into carbopol gel and characterized for texture and rheology profile followed by in vitro and in vivo evaluations. The optimized ACE-NLCs were found to be spherical, nanometric in size with higher drug loading and entrapment efficiency. Results of the in vitro drug release study showed that the developed formulation followed Korsmeyer-Peppas model showing Fickian diffusion. The release was biphasic i.e., initial burst release followed by sustained drug release upto 48 h. The optimized NLCs-based gel formulation showed superior texture, rheological profile and showed better cell uptake efficiency on hyperkeratinocytic cells (HaCaT cell lines) with higher ex vivo skin permeability efficiency vis-a-vis marketed formulation. In conclusion, dermatokinetic modeling and pharmacodynamic study using carrageenan induced edema mice suggests that aceclofenac loaded NLCs hydrogel may provide a better delivery alternative to target various skin layers. (C) 2016 Elsevier B.V. All rights reserved.