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

Journal of Biological Engineering

Review

Gerardo Leyva-Gómez¹  Sheila I. Peña-Corona¹  Alejandra Romero-Montero¹  Sergio A. Bernal-Chávez¹  Héctor Hernández-Parra²  Lashyn Kiyekbayeva³  Javad Sharifi-Rad⁴  Hernán Cortés⁵  Sergio Alcalá-Alcalá⁶  María L. Del Prado-Audelo⁷ 

[1] Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, 04510, Ciudad de México, Mexico;Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, México;Department of Pharmaceutical Technology, Pharmaceutical School, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan;Faculties of Pharmacy, Kazakh-Russian Medical University, Public Health and Nursing, Almaty, Kazakhstan;Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador;Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de Mexico, Mexico;Laboratorio de Tecnología Farmacéutica, Facultad de Farmacia, Universidad Autónoma del Estado de Morelos, 62209, Cuernavaca, Morelos, México;Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Campus Ciudad de México, Ciudad de México, Mexico;

关键词: Drug substances;    Chemical stability;    Physical stability;    Hydrogels;    Chemical properties;    Pharmaceutical applications;   

DOI  :  10.1186/s13036-023-00353-9

 received in 2023-03-10, accepted in 2023-05-15,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

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