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Protein Aggregates in Inhaled Biologics: Challenges and Considerations.
Ibrahim, Mariam; Wallace, Ian; Ghazvini, Saba; Manetz, Scott; Cordoba-Rodriguez, Ruth; Patel, Sajal M.
Afiliación
  • Ibrahim M; Dosage Form Design & Development, Early-Stage Formulation Sciences, Biopharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, USA.
  • Wallace I; Clinical Pharmacology & Safety Sciences, Respiratory & Immunology, Neuroscience, Vaccines & Immune Therapies Safety, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Ghazvini S; Dosage Form Design & Development, Early-Stage Formulation Sciences, Biopharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, USA.
  • Manetz S; Clinical Pharmacology & Safety Sciences, Respiratory & Immunology, Neuroscience, Vaccines & Immune Therapies Safety, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA.
  • Cordoba-Rodriguez R; Regulatory Affairs, Chemistry, Manufacturing and Controls Regulatory Affairs, Oncology R&D, AstraZeneca, Gaithersburg, USA.
  • Patel SM; Dosage Form Design & Development, Early-Stage Formulation Sciences, Biopharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, USA. Electronic address: Sajal.patel@astrazeneca.com.
J Pharm Sci ; 112(5): 1341-1344, 2023 05.
Article en En | MEDLINE | ID: mdl-36796636
Pulmonary delivery is the main route of administration for treatment of local lung diseases. Recently, the interest in delivery of proteins through the pulmonary route for treatment of lung diseases has significantly increased, especially after Covid-19 pandemic. The development of an inhalable protein combines the challenges of inhaled as well as biologic products since protein stability may be compromised during manufacture or delivery. For instance, spray drying is the most common technology for manufacture of inhalable biological particles, however, it imposes shear and thermal stresses which may cause protein unfolding and aggregation post drying. Therefore, protein aggregation should be evaluated for inhaled biologics as it could impact the safety and/or efficacy of the product. While there is extensive knowledge and regulatory guidance on acceptable limits of particles, which inherently include insoluble protein aggregates, in injectable proteins, there is no comparable knowledge for inhaled ones. Moreover, the poor correlation between in vitro setup for analytical testing and the in vivo lung environment limits the predictability of protein aggregation post inhalation. Thus, the purpose of this article is to highlight the major challenges facing the development of inhaled proteins compared to parenteral ones, and to share future thoughts to resolve them.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos Biológicos / COVID-19 Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: J Pharm Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Productos Biológicos / COVID-19 Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: J Pharm Sci Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos