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Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line

By Fulop, G.; Domokos, A.; Galata, D.; Szabo, E.; Gyurkes, M.; Szabo, B.; Farkas, A.; Madarasz, L.; Demuth, B.; Lender, T.; Nagy, T.; Kovacs-Kiss, D.; Van der Gucht, f; Marosi, G.; Nagy, Z. K.

Published on CMKC

Abstract

Highly homogeneous low-dose (50 mu g) 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%).

Journal

International Journal of Pharmaceutics. Volume 594, 2021, 120126

DOI

10.1016/j.ijpharm.2020.120126

Type of publication

Peer-reviewed journal

Affiliations

  • Budapest University of Technology and Economics

Article Classification

Research article

Classification Areas

  • Oral solid dose
  • Process and material characterization

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