Enhancing chemical and physical stability of pharmaceuticals using freeze-thaw method: challenges and opportunities for process optimization through quality by design approach

• Published in: Journal of biological engineering Vol. 17; no. 1; pp. 35 - 18
• Main Authors: Bernal-Chávez, Sergio A., Romero-Montero, Alejandra, Hernández-Parra, Héctor, Peña-Corona, Sheila I., Del Prado-Audelo, María L., Alcalá-Alcalá, Sergio, Cortés, Hernán, Kiyekbayeva, Lashyn, Sharifi-Rad, Javad, Leyva-Gómez, Gerardo
• Format: Journal Article
• Language: English
• Published: London BioMed Central 23.05.2023; BioMed Central Ltd; BMC
• Subjects: Applied Microbiology; Biological Techniques; Biomedical Engineering and Bioengineering; Biotechnology; Chemical bonds; Chemical properties; Chemical stability; Cooling; Crosslinking; Crystallization; Crystals; Cyclodextrin; Cyclodextrins; Design optimization; Dextrins; Drug substances; Emulsions; Engineering; Environmental Engineering/Biotechnology; Freeze-thaw; Heat; Hydrogels; Hydrogen; Methods; Morphology; Nucleic Acid Chemistry; Pharmaceutical applications; Pharmaceuticals; Phase transitions; Physical properties; Physical stability; Physical stress; Polymers; Porosity; Quality management; Review; Spectrum analysis; Stability; Swelling; Technology application; Temperature; Pharmaceutical applications; Chemical properties; Hydrogels; Drug substances; Chemical stability; Physical stability
• ISSN: 1754-1611; 1754-1611
• DOI: 10.1186/s13036-023-00353-9

The freeze-thaw (F/T) method is commonly employed during the processing and handling of drug substances to enhance their chemical and physical stability and obtain pharmaceutical applications such as hydrogels, emulsions, and nanosystems (e.g., supramolecular complexes of cyclodextrins and liposomes). Using F/T in manufacturing hydrogels successfully prevents the need for toxic cross-linking agents; moreover, their use promotes a concentrated product and better stability in emulsions. However, the use of F/T in these applications is limited by their characteristics (e.g., porosity, flexibility, swelling capacity, drug loading, and drug release capacity), which depend on the optimization of process conditions and the kind and ratio of polymers, temperature, time, and the number of cycles that involve high physical stress that could change properties associated to quality attributes. Therefore, is necessary the optimization of F/T conditions and variables. The current research regarding F/T is focused on enhancing the formulations, the process, and the use of this method in pharmaceutical, clinical, and biological areas. The present review aims to discuss different studies related to the impact and effects of the F/T process on the physical, mechanical, and chemical properties (porosity, swelling capacity) of diverse pharmaceutical applications with an emphasis on their formulation properties, the method and variables used, as well as challenges and opportunities in developing. Finally, we review the experimental approach for choosing the standard variables studied in the F/T method applying the systematic methodology of quality by design.