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116d

Top-Spray Fluidised Bed Coating: Scale-up Using Response Surface Methodology

Peter Dybdahl Hede1, Poul Bach1, and Anker D. Jensen2. (1) Solid Products Development, Novozymes A/S, Sm°rmosevej 11, DK-2880, Denmark, (2) Department of Chemical Engineering, Technical University of Denmark, Building 229, DK-2800 Lyngby, Denmark

In the production of solid enzyme products, coating of the enzyme formulation onto inactive filler cores in fluid beds is a common choice. The desired product is thereby a product consisting of unagglomerated individual carrier particles each coated homogeneously with a layer of enzyme. If formulation or process conditions are incorrectly chosen either excessive agglomeration or excessive spray drying of the feed will happen. In both cases a poor product quality is achieved and in any case control of agglomeration is essential during scale-up. Often product and process properties are optimised in small- and medium-scale fluid beds and then transferred to large production-scale. The scale-up of a fluid bed granulation process requires decisions to be made at many levels. Scaling decisions must be closely related to a large number of parameters including: fixed parameters, parameters related to the starting material and the type of fluid bed, input parameters, operating conditions including spraying and mixing conditions as well as processing time etc. With such a variety of interlinked parameters and properties combined with a general lack of fundamental understanding of the granulation process, it is obvious that the scaling of a fluid bed granulation process is a difficult task.

Currently, scaling is still more of an art rather than science being a mix of physics, mathematics, experience, common sense and qualified guesses. A number of different scaling laws and principles have been suggested in principle on either the unit-operation (macro) scale or on the particle-level (micro) scale. Modern scale-up results of fluid bed granulation processes indicate successful scale-up of agglomeration processes from small-scale fluid bed to medium-scale fluid bed in terms of the relative droplet size being the spray rate in g/min divided by the squared air flow through the nozzle in g/min. Thermodynamic studies indicate likewise that the relative humidity as well as the temperature inside the fluid bed vessel during coating are vital properties in respect to agglomeration. Both properties may be combined into a single drying force parameter suggested to be kept constant during scale-up.

The present paper presents fluid bed coating scale-up results in terms of a drying force parameter and a relative droplet parameter defining the agglomeration tendency as the response parameter. Two types of placebo enzyme granule cores are chosen being non-porous glass ballotini cores (180 - 300 ým) and highly porous sodium sulphate cores (180 - 300 ým). Both types of core materials are coated with aqueous solutions of Na2SO4 using Dextrin as binder. Coating experiments are performed in small-scale top-spray fluid bed (GEA Aeromatic-Fielder Strea-1) for various drying force and relative droplet values, each time quantitatively determining the tendency of agglomeration. Based on these results, two response surfaces are derived ľ one for each core material. The prediction of these two models are compared with similar coating experiments performed in a medium-scale fluid bed (MP1). These scale-up results combining thermodynamics with spray conditions and core material porosity may be seen as an important first step towards the development of modern scaling principles combining particle-level properties with fluid bed process conditions.



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