Maniruzzaman Mohammed, Ross Steven A, Dey Tumpa, Nair Arun, Snowden Martin J, Douroumis Dennis
Faculty of Engineering and Science, School of Science, University of Greenwich, Chatham Maritime, Chatham, Kent, ME4 4TB, UK.
Fuji Chemical Industry Co., Ltd., 12F, The Front Tower Shiba Koen, 2-6-3 Shibakoen, Minato-Ward, Tokyo, 105-0011, Japan.
Int J Pharm. 2017 Jun 30;526(1-2):496-505. doi: 10.1016/j.ijpharm.2017.05.020. Epub 2017 May 11.
In this study, a Quality by Design (QbD) approach was used to identify the effect of formulation parameters in a twin screw wet extrusion granulation process for the manufacturing of ibuprofen (IBU) granules with increased dissolution rates. A fractional factorial Design of Experiment (DoE) was used to investigate the effect of the excipient composition, binder amount and liquid to solid (L/S) ratio (independent variables) on drug dissolution rates, median particle size diameter and specific surface area (dependent variables). The intra-granular addition of the binder in inorganic/polymer blends processed with ethanol as granulating liquids facilitated the formation of granules at various particle sizes. DoE regression analysis showed that all formulation parameters affect the dependent variables significantly. The enhanced dissolution rates were attributed not only to the IBU particle size reduction and adsorption in the porous inorganic network but also to the high specific surface area of the produced granules. Dynamic vapour sorption showed increased water absorption for granules with small particle size distribution and high specific surface area.
在本研究中，采用质量源于设计（QbD）方法来确定在双螺杆湿法制粒工艺中，制剂参数对布洛芬（IBU）颗粒溶出速率提高的影响。采用部分因子实验设计（DoE）来研究辅料组成、粘合剂用量和液固比（自变量）对药物溶出速率、中位粒径和比表面积（因变量）的影响。在以乙醇作为制粒液体处理的无机/聚合物共混物中，粘合剂的粒内添加促进了各种粒径颗粒的形成。DoE回归分析表明，所有制剂参数均对因变量有显著影响。溶出速率的提高不仅归因于IBU粒径减小以及在多孔无机网络中的吸附，还归因于所制得颗粒的高比表面积。动态蒸汽吸附表明，粒径分布小且比表面积高的颗粒吸水性增强。
