Effects on the Quality of Granules Obtained in Conventionally Designed Fluid-bed Equipment Compared to Granules Obtained in a Washing In Place / Cleaning In Place Designed Unit
Axel Schiffmanna, Jochen A. Dresslerb, Bernhard Luyb, and Hans Leuenbergera
University of Basel, Pharmacenter, Institute of Pharmaceutical Technologya, Basel (Switzerland), and Glatt GmbH, Technology Process Centerb, Binzen (Germany)
Due to increasing demands for an automated cleanability of processing equipment, equipment manufacturers have improved their product design for an optimum performance of the Cleaning In Place (CIP) process with respect to GMP standards. In this context it is important to assess if and eventually how these design improvements do effect the properties of granules manufactured in this fluid-bed system. Besides other design variations especially the bottom plate and the product retention filters are considered as critical magnitudes of influ-ence in a fluid-bed process. The conventional product retaining filter system used for this study consist of a seamed polyester fabric with a mesh size of approximately 20 µm. During a process this type of cloth filter is cleaned by means of pneumatic shaking cylinders which gen-erate a periodically up and down movement of the bag type filter unit for a specified time. The product recovery filters developed for a WIP/CIP process are cylindrical filter cartridges consisting of stainless steel material with a mesh size of 10 µm in this study. Instead of the up an down movement the novel cartridges are periodically purged with bursts of compressed air at a pressure of 6 bar.
The study compares standard granule material obtained in a fluid-bed top spray granulator which was modified for a better cleanability during a WIP/CIP process with granules obtained in a conventionally designed unit. The granula-tions are carried out under equal process conditions with the same formulation. The goal of this study is to detect eventual differences between the granule properties. For the comparison of the quality of the granule properties the bulk and tapped density, loss on drying, angle of repose, particle size distribution and the uniformity of drug content were measured. Scanning Electron Micrographs were prepared to visualize possible morphological differences. Within this study it can be concluded that a top-spray granulation process optimized in a conventionally designed unit can be transferred to a WIP/CIP designed fluid-bed granulator without changing process variables. The investigated design im-provements do not affect the granule quality.
Key words CIP (Cleaning In Place) • Fluid-bed granulator, equipment design • Granulation, granule quality, influence of processing equipment • WIP (Washing In Place)