The Development of a Novel Aflibercept Formulation for Ocular Delivery.
J Pharm Sci
; 113(2): 366-376, 2024 02.
Article
en En
| MEDLINE
| ID: mdl-38042344
ABSTRACT
Aflibercept is a recombinant fusion protein that is commercially available for several ocular diseases impacting millions of people worldwide. Here, we use a case study approach to examine alternative liquid formulations for aflibercept for ocular delivery, utilizing different stabilizers, buffering agents, and surfactants with the goal of improving the thermostability to allow for limited storage outside the cold chain. The formulations were developed by studying the effects of pH changes, substituting amino acids for sucrose and salt, and using polysorbate 80 or poloxamer 188 instead of polysorbate 20. A formulation containing acetate, proline, and poloxamer 188 had lower rates of aggregate formation at 4, 30, and 40°C when compared to the marketed commercial formulation containing phosphate, sucrose, sodium chloride, and polysorbate 20. Further studies examining subvisible particles after exposure to a transport stress and long-term stability at 4°C, post-translational modifications by multi-attribute method, purity by reduced and non-reduced capillary electrophoresis, and potency by cell proliferation also demonstrated a comparable or improved stability for the enhanced formulation of acetate, proline, and poloxamer 188. This enhanced stability could enable limited storage outside of the cold chain, allowing for easier distribution in low to middle income countries.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polisorbatos
/
Poloxámero
/
Receptores de Factores de Crecimiento Endotelial Vascular
Límite:
Humans
Idioma:
En
Revista:
J Pharm Sci
Año:
2024
Tipo del documento:
Article