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

• Published in: Pharmaceutical research 2022-09, Vol.39 (9), p.2017-2031
• Main Authors: Navrátil, Ondřej, Kolář, Jiří, Zadražil, Aleš, Štěpánek, František
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Coatings; Computer applications; Dielectric films; Diffusion coefficient; Drying; Evaporation; Heat transfer; Mass transfer; Mathematical models; Medical Law; Methylcellulose; Model-Guided Process Development; Original Research Article; Pharmaceuticals; Pharmacology/Toxicology; Pharmacy; Polymers; Solvents; Thin film coatings; Thin films; Vinylpyrrolidone
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-022-03352-5

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.