Preclinical modeling of intravitreal suspensions

Area of Science:

• Ophthalmology
• Pharmaceutical Sciences
• Drug Delivery

Background:

• Developing intravitreal small molecule therapies faces challenges, including the need for complex polymer depot formulations.
• Complex formulations require significant time and material investment, often unavailable during early preclinical development.

Purpose of the Study:

• To present a diffusion-limited pseudo-steady state model for predicting drug release from intravitreal suspension formulations.
• To aid preclinical formulators in determining the necessity of complex formulations versus simple suspensions.

Main Methods:

• A diffusion-limited pseudo-steady state model was developed and applied.
• The model predicted the intravitreal performance of triamcinolone acetonide and GNE-947 in rabbit eyes.
• Model predictions were also made for a marketed formulation of triamcinolone acetonide in humans.

Main Results:

• The model provides predictions for drug release kinetics from intravitreal suspensions.
• It allows for evaluation of different molecules and dose levels in preclinical models.
• The model can forecast the performance of established formulations in human subjects.

Conclusions:

• The presented model offers a valuable tool for preclinical drug formulation development for intravitreal therapies.
• It can guide decisions regarding formulation complexity, potentially saving time and resources.
• This approach supports more confident formulation selection for supporting study designs.