Solution formulation development of a VEGF inhibitor for intravitreal injection

Area of Science:

• Ophthalmology
• Pharmaceutics
• Drug Delivery

Background:

• Age-related macular degeneration (AMD) is a leading cause of vision loss.
• Vascular Endothelial Growth Factor Receptors (VEGFRs) are key targets for AMD treatment.
• Sustained drug delivery to the vitreous humor is challenging.

Purpose of the Study:

• To develop an ophthalmic solution formulation of PF-00337210 for intravitreal injection.
• To achieve sustained drug delivery through in situ precipitation in the vitreous.
• To optimize formulation parameters considering safety and efficacy for intravitreal administration.

Main Methods:

• Characterization of PF-00337210 aqueous solubility and pH dependence.
• Buffer stressing studies and chemical/physical stability assessments.
• Development and testing of an isotonic, citrate-buffered formulation with NaCl for tonicity.

Main Results:

• A stable ophthalmic formulation of PF-00337210 (up to 60 mg/mL) was successfully developed.
• The formulation demonstrated reproducible precipitation upon simulated intravitreal injection, forming a depot.
• The active drug, PF-00337210, acts as the precipitating agent for sustained release.

Conclusions:

• This study presents the first nonpolymeric, in situ-forming depot formulation for intravitreal delivery.
• The developed formulation enables sustained release of PF-00337210, a potent VEGFR inhibitor.
• This approach offers a promising strategy for managing age-related macular degeneration.