Preclinical modeling of intravitreal suspensions

There are a number of obstacles that complicate the development of intravitreal delivered small molecules therapies. One serious complication is the potential need for complex polymer depot formulations early in the drug discovery process. The development of such formulations often requires substantial investment of time and material which may not be readily available in preclinical development. Herein I present a diffusion limited pseudo-steady state model to provide prediction of drug release from an intravitreally administered suspension formulation. By using such a model, a preclinical formulator may be able to more confidently determine if development of a complex formulation is required or if a simple suspension may work to support a study design. In this report, the model is used to predict the intravitreal preformance of two different molecules (triamcinolone acetonide and GNE-947) at multiple dose levels in rabbit eyes as well as provide a prediction for the performance of a marketed formulation of Trimacinolone Acetonide in humans.