Development and practical application of a computational model of the pelletizing process in a fluidized bed

Introduction. Controlling the generation of the distribution of the properties of product granules, in particular the size distribution, density and morphology of particles in wet granulation technology is a complex process in which a number of phenomena occur simultaneously, which collectively control the specified pharmaceutical and technological properties of mixtures. The developed computational model of the granulation process will allow you to create and design processes with a reduced cost level of expensive, time-consuming experimental verification at various scales of work. Understanding how to evenly distribute the binder using a computational model will not only help control the distribution of granule nuclei, but will also lead to a more manageable technological process. One of the criteria for a stable calculation model of the granulation process is the reduction of illiquid batches of products that do not meet specifications.

Aim. Application of the developed computational model to optimize the granulation process of solid dosage forms.

Materials and methods. To develop a computational model of the granulation process, formulas for determining the bulk density before and after compaction, the wetting edge angle, bulk density, effective porosity, the Kozeni – Karman hydrodynamics equations, the modified Lucas – Washburn differential equation, the equations of spray velocity and particle motion in the spray zone, the time of penetration of a drop into a powder layer and the dimensionless spray flow. The object of the experimental confirmation of the developed computational model of the granulation process was the powder of a medicinal product containing an active pharmaceutical substance based on a derivative of 3,7-diazabicyclo[3.3.1]nonan – TST-9 and subject to further tableting. The following liquids were considered as humidifiers in experimental studies: purified water and hypromellose solution. The viscosity of the samples was measured using a vibration viscometer SV-10 (A&D, Japan). Experimental granulation was carried out in an installation with a fluidized bed. To determine the quality indicators of the mixture and granules, a manual flowability tester with a digital height meter EFT-01 (Electrolab, India) and a bulk density tester were used ETD-1020 (Electrolab, India). The surface tension of granulating liquids was measured on a K6 tensiometer using the ring separation method (the due Nui method) (KRÜSS GmbH, Germany).

Results and discussion. An algorithm is presented for calculating the parameters of the computational model of the granulation process, the time of droplet penetration, which is controlled by the pharmaceutical and technological characteristics of the composition of the dosage form, and the dimensionless spray flow, which is regulated by the process parameters. Their established values made it possible to predict the behavior of granules and product yield.

Conclusion. In this paper, the application of a computational model for the predicted production of granules is demonstrated by the example of the development of a technology for obtaining a drug based on an active pharmaceutical substance that is a derivative of 3,7-diazabicyclo[3.3.1]nonan – TST-9. As a result, the projected values of the computational model were confirmed in experimental studies of granulation in a fluidized bed installation using various moisturizing liquids.

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