In vitro Release Profiles of Atrigel® Sustained Release Formulations

Abstract

Purpose: : The Atrigel^® drug delivery system consists of biodegradable polymers dissolved in biocompatible carriers. Pharmaceuticals may be blended into this liquid delivery system at the time of manufacturing or, depending upon the product, may be added later by the physician at the time of use. When the liquid product is injected through a small gauge needle or placed into accessible tissue sites through a cannula, water in the tissue fluids causes the polymer to precipitate and trap the drug in a solid implant. The drug encapsulated within the implant is then released in a controlled manner as the polymer matrix biodegrades with time. Adjustment of the formulation allows for a programmable drug release rate. The purpose of this study was to establish an in–vitro, in–vivo correlation (IVIVC) of delivery using Atrigel^®. The ocular environment is predominantly water, containing 1% collagen and hyaluronic acid, and is a relatively static and contained system. To this end, we studied an in vitro model to evaluate QLT090354 drug release into simulated vitreous.

Methods: : The drug active QLT090354 and various Atrigel^® polymer combinations were injected using Hamilton syringes into simulated vitreous to form an implant. The formulations were also injected subcutaneously into rats or intravitreally into rabbit eyes for an in vivo comparison. Following injection, the QLT090354 content in the implants and reservoir was determined by HPLC.

Results: : Various implant sizes were chosen to represent a range of intravitreal injection volumes. All sizes of implants were reproducibly injected. The collective mass balance recovery of in vitro implants and reservoir samples was satisfactory and drug release by implant extraction was corroborated by release resulting from assayed reservoir samples. The release of compound from in vivo implants and those formed in vitro were comparable.

Conclusions: : Atrigel^® implants formed in vitro were used to predict the in vivo release of QLT090354.

Keywords: vitreous • retina