Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Eur J Pharm Biopharm. 2012 Sep;82(1):205-11. doi: 10.1016/j.ejpb.2012.05.010. Epub 2012 Jun 9.
The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, α-lactose monohydrate and PVP (ratio: 30/67.5/2.5,w/w) was granulated with demineralized water. Experiments were done using the high-shear wet granulation module (based on twin screw granulation) of the ConsiGma™-25 unit (a continuous tablet manufacturing system) for particle size enlargement. After drying, granules were compressed using a MODUL™ P tablet press (compression force: 10 kN, tablet diameter: 12 mm). Using a D-optimal experimental design, the effect of several process variables (throughput (10-25 kg/h), screw speed (600-950 rpm), screw configuration (number (2, 4, 6 and 12) and angle (30°, 60° and 90°) of kneading elements), barrel temperature (25-40°C) and method of binder addition (dry versus wet)) on the granulation process (torque and temperature increase in barrel wall), granule (particle size distribution, friability and flowability) and tablet (tensile strength, porosity, friability, disintegration time and dissolution) quality was evaluated. The results showed that the quality of granules and tablets can be optimized by adjusting specific process variables (number of kneading elements, barrel temperature and binder addition method) during a granulation process using a continuous twin screw granulator.
本研究的目的是筛选茶碱（125mg）片剂，通过双螺杆造粒来提高工艺理解和确定颗粒和片剂质量的工艺变量的知识。将茶碱无水物、α-乳糖一水合物和 PVP（比例：30/67.5/2.5，w/w）的预混物用去离子水造粒。实验是在 ConsiGma™-25 单元（连续片剂制造系统）的高剪切湿法制粒模块（基于双螺杆造粒）中进行的，用于粒径增大。干燥后，使用 MODUL™ P 压片机（压缩力：10kN，片剂直径：12mm）将颗粒压缩。使用 D-最优实验设计，研究了几个工艺变量（产量（10-25kg/h）、螺杆速度（600-950rpm）、螺杆结构（捏合元件的数量（2、4、6 和 12）和角度（30°、60°和 90°））、机筒温度（25-40°C）和粘合剂添加方法（干法与湿法））对造粒过程（机筒壁扭矩和温度升高）、颗粒（粒度分布、脆性和流动性）和片剂（拉伸强度、孔隙率、脆性、崩解时间和溶解）质量的影响。结果表明，通过调整连续双螺杆造粒过程中的特定工艺变量（捏合元件数量、机筒温度和粘合剂添加方法），可以优化颗粒和片剂的质量。
