Diffusion, Kinetics, And Thermal Transport in Sol–Gel–Derived Pharmaceutical Manufacturing Technique: An Applied Physics Review
Keywords:
Sol-gel, Fickian Diffusion, predictive models, CFDAbstract
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).
References
Adepu, S., & Ramakrishna, S. (2021). Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules (Basel, Switzerland), 26(19), 5905. https://doi.org/10.3390/molecules26195905
Boel, E., Koekoekx, R., Dedroog, S., Babkin, I., Vetrano, M. R., Clasen, C., & Van den Mooter, G. (2020). Unraveling Particle Formation: From Single Droplet Drying to Spray Drying and Electrospraying. Pharmaceutics, 12(7), 625. https://doi.org/10.3390/pharmaceutics12070625
Espinosa, M. A. (2021). Thermodynamics and kinetics of sol-gel transition: Effects of nanoconfinement (Doctoral dissertation, University of Alabama at Birmingham). All ETDs from UAB, 783. https://digitalcommons.library.uab.edu/etd-collection/783
Ezike, T. C., Okpala, U. S., Onoja, U. L., Nwike, C. P., Ezeako, E. C., Okpara, O. J., Okoroafor, C. C., Eze, S. C., Kalu, O. L., Odoh, E. C., Nwadike, U. G., Ogbodo, J. O., Umeh, B. U., Ossai, E. C., & Nwanguma, B. C. (2023). Advances in drug delivery systems, challenges and future directions. Heliyon, 9(6), e17488. https://doi.org/10.1016/j.heliyon.2023.e17488
Fu, Y., & Kao, W. J. (2009). Drug release kinetics and transport mechanisms from semi-interpenetrating networks of gelatin and poly(ethylene glycol) diacrylate. Pharmaceutical research, 26(9), 2115–2124. https://doi.org/10.1007/s11095-009-9923-1
Lach, Ł., & Svyetlichnyy, D. (2024). Recent Progress in Heat and Mass Transfer Modeling for Chemical Vapor Deposition Processes. Energies, 17(13), 3267. https://doi.org/10.3390/en17133267
Li, P., Ma, C., Chen, Z., Wang, H., Wang, Y., & Bai, H. (2023). A Review: Study on the Enhancement Mechanism of Heat and Moisture Transfer in Deformable Porous Media. Processes, 11(9), 2699. https://doi.org/10.3390/pr11092699
Merghes, P., Ilia, G., Maranescu, B., Varan, N., & Simulescu, V. (2024). The Sol-Gel Process, a Green Method Used to Obtain Hybrid Materials Containing Phosphorus and Zirconium. Gels (Basel, Switzerland), 10(10), 656. https://doi.org/10.3390/gels10100656
Mohanan, S., Guan, X., Liang, M., Karakoti, A., & Vinu, A. (2024). Stimuli-responsive silica silanol conjugates: Strategic nanoarchitectonics in targeted drug delivery. Small, 20(39), 1–29. https://doi.org/10.1002/smll.202301113
Musil, F., Grisafi, A., Bartók, A. P., Ortner, C., Csányi, G., & Ceriotti, M. (2021). Physics-inspired structural representations for molecules and materials. Chemical Reviews, 121(16), 9759–9815. https://doi.org/10.1021/acs.chemrev.1c00021
Nadamani, M. N., Shadloo, M. S., & Dbouk, T. (2025). A Review on Theoretical and Computational Fluid Dynamics Modeling of Coupled Heat and Mass Transfer in Fixed Beds of Adsorbing Porous Media. Energies, 18(24), 6418. https://doi.org/10.3390/en18246418
Rabby, M. I. I., Uddin, M. W., Hossain, F., & Ul-Iman, S. (2024). Impact of non-uniform heat flux conditions on convective heat transfer and energy efficiency in a corrugated tube. Heliyon, 10(11), e31663. https://doi.org/10.1016/j.heliyon.2024.e31663
Robnik, B., Likozar, B., Wang, B., Stanić Ljubin, T., & Časar, Z. (2019). Understanding and Kinetic Modeling of Complex Degradation Pathways in the Solid Dosage Form: The Case of Saxagliptin. Pharmaceutics, 11(9), 452. https://doi.org/10.3390/pharmaceutics11090452
Schiller, J., Naji, L., Trampel, R., Ngwa, W., Knauss, R., & Arnold, K. (2004). Pulsed-field gradient-nuclear magnetic resonance (PFG NMR) to measure the diffusion of ions and polymers in cartilage: applications in joint diseases. Methods in molecular medicine, 101, 287–302. https://doi.org/10.1385/1-59259-821-8:287
Seidel, S., Mozaffari, F., Maschke, R. W., Kraume, M., Eibl-Schindler, R., & Eibl, D. (2023). Automated Shape and Process Parameter Optimization for Scaling Up Geometrically Non-Similar Bioreactors. Processes, 11(9), 2703. https://doi.org/10.3390/pr11092703
Sinkó K. (2010). Influence of Chemical Conditions on the Nanoporous Structure of Silicate Aerogels. Materials, 3(1), 704–740. https://doi.org/10.3390/ma3010704
Szczyglewska, P., Feliczak-Guzik, A., & Nowak, I. (2023). Nanotechnology-General Aspects: A Chemical Reduction Approach to the Synthesis of Nanoparticles. Molecules (Basel, Switzerland), 28(13), 4932. https://doi.org/10.3390/molecules28134932
Workman, J. Jr. (2024). A review of the latest research applications using FT-IR spectroscopy. Spectroscopy, 39(Suppl. 8), 22–28. https://doi.org/10.56530/spectroscopy.ak9689m8
Zhang, G., Li, C., Wang, Y., Lin, L., & Ostrikov, K. (2023). High-Performance Methylsilsesquioxane Aerogels: Hydrolysis Mechanisms and Maximizing Compression Properties. Gels, 9(9), 720. https://doi.org/10.3390/gels9090720
