Integrated Twin-Screw Wet Granulation, Continuous Vibrational Fluid Drying and Milling: A fully continuous powder to granule line

Highly homogeneous low-dose (50 µg) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a Continuous Sieving (CS) unit. Throughout the experiments a pre-blend of lactose-monohydrate and corn starch was gravimetrically dosed with 1 kg/h into the TSWG, where they were successfully granulated with the drug containing water-based PVPK30 solution.

The wet mass was subsequently dried in the CFBD on a vibratory conveyor belt and finally sieved in the milling unit. Granule production efficiency was maximized by determining the minimal Liquid-to-Solid (L/S) ratio (0.11). Design of Experiments (DoE) were carried out in order to evaluate the influence of the drying process parameters of the CFBD on the Loss-on-Drying (LOD) results. The manufactured granules were compressed into tablets by an industrial tablet rotary press with excellent API homogeneity (RSD < 3%). Significant scale-up was realized with the CM line by increasing the throughput rate to 10 kg/h.

The manufactured granules yielded very similar results to the previous small-scale granulation runs. API homogeneity was demonstrated (RSD < 2%) with Blend Uniformity Analysis (BUA). The efficiency of TSWG granulation was compared to High-Shear Granulation (HSG) with the same L/S ratio. The final results have demonstrated that both the liquid distribution and more importantly API homogeneity was better in case of the TSWG granulation (RSD 1.3% vs. 4.5%).

Open access: G. Fülöp, A. Domokos, D. Galata, E. Szabó, M. Gyürkés, B. Szabó, A. Farkas, L. Madarász, B. Démuth, T. Lendér, T. Nagy, D. Kovács-Kiss, F. Van der Gucht, G. Marosi, Z.K. Nagy,
Integrated Twin-Screw Wet Granulation, Continuous Vibrational Fluid Drying and Milling: A fully continuous powder to granule line, International Journal of Pharmaceutics, 2020, 120126, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2020.120126

Materials
Carvedilol (CAR), α-lactose monohydrate (GranuLac® 70), Povidone, PVPK30 (Kollidon® 30), corn starch