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Model-Based Evaluation of Drying Kinetics and Solvent Diffusion in Pharmaceutical Thin Film Coatings

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Abstract

Purpose

Fluid-bed coating processes make it possible to manufacture pharmaceutical products with tuneable properties. The choice of polymer type and coating thickness provides control over the drug release characteristics, and multi-layer pellet coatings can combine several active ingredients or achieve tailored drug release profiles. However, the fluid-bed coating is a parametrically sensitive process due to the simultaneous occurrence of polymer solution spraying and solvent evaporation. Designing a robust fluid-bed coating process requires the knowledge of thin film drying kinetics, which in turn critically depends on an accurate description of concentration-dependent solvent diffusion in the polymer.

Methods

This work presents a mathematical model of thin film drying as an enabling tool for fluid-bed process design. A custom-built benchtop drying cell able to record and evaluate the drying kinetics of a chosen polymeric excipient has been constructed, validated, and used for data collection.

Results

A semi-empirical mathematical model combining heat transfer, mass transfer, and film thickness evolution was formulated and used for estimating the solvent diffusion coefficient and solvent distribution in the polymer layer. The combined experimental and computational methodology was then used for analysing the drying kinetics of common polymeric excipients: poly(vinylpyrrolidone) and two grades of hydroxypropyl methylcellulose.

Conclusions

The experimental setup together with the mathematical model represents a valuable tool for predictive modeling of pharmaceutical coating processes.

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Funding

F.Š. and A.Z. would like to thank the Czech Science Foundation (EXPRO grant no. 19-26127X) for financial support. O.N. and J.K. would like to acknowledge support by The Pharmaceutical Applied Research Centre.

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Authors and Affiliations

  1. Department of Chemical Engineering, University of Chemistry and Technology Prague, Technicka 3, 166 28, Prague 6, Czech Republic

    Ondřej Navrátil, Jiří Kolář, Aleš Zadražil & František Štěpánek

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  1. Ondřej Navrátil
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  2. Jiří Kolář
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  3. Aleš Zadražil
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  4. František Štěpánek
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Contributions

O.N.: Experimental design, data acquisition, model development, data analysis, manuscript writing.

J.K.: Model development, data analysis, manuscript writing.

A.Z.: Experimental design, data acquisition, manuscript writing.

F.Š.: Conception, supervision, manuscript writing.

Corresponding author

Correspondence to František Štěpánek.

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The authors declare no conflict of interest.

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Navrátil, O., Kolář, J., Zadražil, A. et al. Model-Based Evaluation of Drying Kinetics and Solvent Diffusion in Pharmaceutical Thin Film Coatings. Pharm Res 39, 2017–2031 (2022). https://doi.org/10.1007/s11095-022-03352-5

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  • DOI: https://doi.org/10.1007/s11095-022-03352-5

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