Diffusion, Kinetics, And Thermal Transport in Sol–Gel–Derived Pharmaceutical Manufacturing Technique: An Applied Physics Review

Abstract

Sol-gel (S-G) provides an attractive, low-temperature approach for encapsulating sensitive drugs and has thus become a key method in the modern pharmaceutical manufacturing. Yet successful industrialization depends on being able to control the basic laws of physics underpinning formation and properties of materials. This review in applied physics compiles and distills recent literature around these three interacting pillars—diffusion, reaction kinetics, and thermal transport. Drug release kinetics are controlled by the diffusion mechanisms, following non-Fickian behavior modulated by matrix porosity and drug–matrix interaction. The kinetics of the reaction (pH-dependent hydrolysis and condensation) itself program the final material structure, density, and longer-term hydrolytic and chemical stability of the encapsulated payload. Thermal transport and heat/mass coupling during drying constitute the principal engineering problem: uncontrolled gradients lead to internal stresses, cracking and unacceptable heterogeneities of batches. We believe the rational design, scale-up and robust, compliant drug product manufacturing of S-G derived pharmaceutical products necessitates the integration of predictive tools (e.g., computational fluid dynamics and advanced in situ characterization).

Keywords:

Sol-gel, Fickian Diffusion, predictive models, CFD

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