Development of monoclonal antibodies in tablet form: A new approach for local delivery

• Published in: International journal of pharmaceutics Vol. 661; p. 124423
• Main Authors: Auffray, Julie, Hsein, Hassana, Biteau, Nicolas, Velours, Christophe, Noël, Thierry, Tchoreloff, Pierre
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.08.2024
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - chemistry; Biological activity; Chemistry, Pharmaceutical - methods; Drug Compounding - methods; Drug Delivery Systems - methods; Drug Stability; Excipients - chemistry; Freeze Drying; Life Sciences; Local delivery; Microbiology and Parasitology; Monoclonal antibody; Oral delivery; Powders; Sucrose - chemistry; Tablet; Tablets; Trehalose - chemistry; Local delivery; Tablet; Monoclonal antibody; Freeze-drying; Biological activity; Oral delivery; Excipients; Powders; Tablets; Trehalose; Sucrose; Drug Stability; Freeze Drying; Antibodies; Pharmaceutical; Drug Delivery Systems; Chemistry; Drug Compounding; Monoclonal
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124423

[Display omitted] Among the various pharmaceutical forms, tablets offer numerous advantages, like ease of administration, cost-effectiveness in production, and better stability of biomolecules. Beyond these benefits, the tablet form opens up possibilities for alternative routes for the local delivery of biopharmaceuticals such as oral or vaginal administration, thereby expanding the therapeutic applications of these biomolecules and overcoming the inconvenients associated with parenteral administration. However, to date there is limited information on the feasibility of developing biomolecules in the tablet form. In this study, we have evaluated the feasibility of developing monoclonal antibodies in the tablet form while preserving their biological properties. Different excipients and process parameters were studied to assess their impact on the antibody’s integrity during tableting. ELISA results show that applying compression pressure up to 100 MPa is not detrimental to the antibody’s binding properties when formulated from a lyophilized powder containing trehalose or sucrose as the major excipient. This observation was confirmed with SPR and ultracentrifugation experiments, which demonstrated that neither the binding affinity for both Fc and Fab antibody fragments nor its aggregation rate are affected by the tableting process. After compression, the tablets containing the antibodies have been shown to be stable for 6 months at room temperature.