Adrian Schmidt1,2, Hans de Waard2, Peter Kleinebudde1, Markus Krumme3. 1. Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, 40225, Duesseldorf, Germany. 2. Novartis AG, WSJ-027.4.015, Novartis Campus, 4002, Basel, Switzerland. 3. Novartis AG, WSJ-027.4.015, Novartis Campus, 4002, Basel, Switzerland. Markus.Krumme@novartis.com.
Abstract
PURPOSE: It was investigated if continuous wet granulation and drying could be combined in a twin-screw granulator with the aim to provide (pre-)dried granules in a single-step process, i.e. in-barrel-drying. METHODS: To have a consistent and robust material propulsion mechanism, a twin-screw granulator was divided into two compartments. One compartment was operated at lower temperature to granulate and to pre-heat the material, while another compartment was operated at very high temperature to evaporate the granulation liquid as rapidly as possible. Design of experiments was used to investigate the in-barrel-drying process in detail. The process was further investigated for twin-screw wet granulation with API suspension feed, and compared against traditional fluidised-bed drying. Granule and compact properties were evaluated to study the process impact on the product quality. RESULTS: In-barrel-drying was demonstrated as feasible and yielded completely dried and granulated material at specific settings. The evaporation zone temperature and the processed mass of water were identified as key parameters to balance the evaporation capacity of the process and the material throughput. Granules and compacts showed an acceptable product quality. CONCLUSIONS: In-barrel-drying can be used to condense the wet granulation and drying process steps into one piece of equipment, thereby limiting or even omitting downstream drying process steps.
PURPOSE: It was investigated if continuous wet granulation and drying could be combined in a twin-screw granulator with the aim to provide (pre-)dried granules in a single-step process, i.e. in-barrel-drying. METHODS: To have a consistent and robust material propulsion mechanism, a twin-screw granulator was divided into two compartments. One compartment was operated at lower temperature to granulate and to pre-heat the material, while another compartment was operated at very high temperature to evaporate the granulation liquid as rapidly as possible. Design of experiments was used to investigate the in-barrel-drying process in detail. The process was further investigated for twin-screw wet granulation with API suspension feed, and compared against traditional fluidised-bed drying. Granule and compact properties were evaluated to study the process impact on the product quality. RESULTS: In-barrel-drying was demonstrated as feasible and yielded completely dried and granulated material at specific settings. The evaporation zone temperature and the processed mass of water were identified as key parameters to balance the evaporation capacity of the process and the material throughput. Granules and compacts showed an acceptable product quality. CONCLUSIONS: In-barrel-drying can be used to condense the wet granulation and drying process steps into one piece of equipment, thereby limiting or even omitting downstream drying process steps.
Entities:
Keywords:
API suspension feed; design of experiments; fluidised-bed drying; telescoped process; twin-screw wet granulation
Authors: Barry Crean; Xinyong Chen; Simon R Banks; Walter G Cook; Colin D Melia; Clive J Roberts Journal: Pharm Res Date: 2009-02-03 Impact factor: 4.200