Stability and repeatability of a continuous twin screw granulation and drying system

• Published in: European journal of pharmaceutics and biopharmaceutics 2013-11, Vol.85 (3), p.1031-1038
• Main Authors: Vercruysse, J., Delaet, U., Van Assche, I., Cappuyns, P., Arata, F., Caporicci, G., De Beer, T., Remon, J.P., Vervaet, C.
• Format: Article
• Language: English
• Subjects: Cellulose - chemistry; Chemistry, Pharmaceutical - methods; Continuous production; Continuous twin screw granulation and drying; Drug Compounding - methods; Excipients - chemistry; Granule and tablet quality; Particle Size; Powders - chemistry; Pressure; Process transfer; Repeatability; Reproducibility of Results; Solubility; Stability; Starch - analogs & derivatives; Starch - chemistry; Tablets - chemistry; Temperature
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2013.05.002

The aim of this study was to investigate the process transfer of a commercially available product from the current batch fluid bed granulation and drying production method to an innovative continuously operating “from powder to tablet” production line using twin screw granulation as an intermediate granulation step. By monitoring process outcomes (torque, water temperature at the granulator jacket inlet, differential pressure over the dryer filters, and temperature mill screen) and granule and tablet quality in function of process time, the stability and repeatability during long production runs were determined. Three consecutive 5h “from powder to tablet” production runs were performed using the ConsiGma™-25 system (GEA Pharma Systems, Collette™, Wommelgem, Belgium). A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch, and sodium starch glycolate was granulated with distilled water. After drying and milling (1000μm and 800rpm), granules were in-line blended with magnesium stearate and directly compressed using a Modul™ P tablet press (tablet weight: 430mg, main compression force: 12kN). Granule (loss on drying, particle size distribution, friability, flow) and tablet (weight uniformity, hardness, thickness, friability, content uniformity, disintegration time, and dissolution) quality was evaluated in function of process time. For each of the logged process outcomes, a stabilization period was needed to reach steady-state conditions. Slightly deviating particle size distribution and friability results for milled granules were observed during start-up due to initial layering of the mill screen. However, no deviating tablet quality was detected in function of process time. For multiple hours, granule and tablet quality was constant in function of process time. Furthermore, process data trends were highly repeatable. Consequently, the ConsiGma™-25 system can be considered as a stable and repeatable system for the continuous production of tablets via wet granulation.