title: Stability and repeatability of a continuous twin screw granulation and drying system.
abstract: 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 (1000 μm and 800 rpm), granules were in-line blended with magnesium stearate and directly compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). 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.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Vercruysse
authors.forename: U
authors.initials: U
authors.lastname: Delaet
authors.forename: I
authors.initials: I
authors.lastname: Van Assche
authors.forename: P
authors.initials: P
authors.lastname: Cappuyns
authors.forename: F
authors.initials: F
authors.lastname: Arata
authors.forename: G
authors.initials: G
authors.lastname: Caporicci
authors.forename: T
authors.initials: T
authors.lastname: De Beer
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D011312:Pressure; D015203:Reproducibility of Results; D012995:Solubility; D013213:Starch / Q000031:analogs & derivatives / Q000737:chemistry; D013607:Tablets / Q000737:chemistry; D013696:Temperature
chemical_list: D005079:Excipients; D011208:Powders; D013607:Tablets; D002482:Cellulose; D013213:Starch; C048390:sodium starch glycolate
keywords: Continuous production; Continuous twin screw granulation and drying; Granule and tablet quality; Process transfer; Repeatability; Stability