Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters

Publication date: 30 May 2016 Source:International Journal of Pharmaceutics, Volume 505, Issues 1–2 Author(s): V. Vanhoorne, B. Vanbillemont, J. Vercruysse, F. De Leersnyder, P. Gomes, T. De Beer, J.P. Remon, C. Vervaet The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fine...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research