Influence of Storage Temperature on Sustained Release Dexamethasone Pharmacokinetics in a Beagle Model

Abstract

 

Purpose

 

To evaluate the influence of elevated storage temperature on the release of dexamethasone from a bioresorbable hydrogel punctum plug in a beagle model.

 

Methods

 

The Sustained Release Dexamethasone Punctum Plug (OTX-DP) is comprised of dexamethasone suspended in a bioresorbable polyethylene glycol (PEG) hydrogel matrix and sized for insertion into the vertical canaliculus. Upon insertion, the hydrogel swells to conform to the canaliculus ensuring plug retention. Sustained release of dexamethasone occurs while the plug is retained in the canaliculus. Following treatment, the OTX-DP degrades via hydrolysis and is resorbed.<br /> <br /> OTX-DP samples from a single lot were separated into two test groups. The first test group was stored at refrigerated storage conditions (5 °C) and the second test group was stored at stress conditions (40 °C / 75% RH); each for a period of 3 months. Samples from each group were inserted into beagle canaliculi, with one plug inserted per eye (n=20 eyes per test group). Tear film samples were collected from each test group using Schirmer test strips over a 7 week period and analyzed via HPLC/MS/MS to determine dexamethasone concentrations at each time point.

 

Results

 

The mean concentrations along with the standard errors of dexamethasone in tear film samples were plotted for each test group, as shown in Figure One. The plotted results showed no meaningful difference in in vivo drug release profile over the duration of the study. Each test group maintained >200 ng/mL of dexamethasone in the tear film through 21 days.

 

Conclusions

 

Elevated temperature exposure of drug products can result in differences in product performance with respect to dose delivery. Our results demonstrate no meaningful difference in tear film levels of dexamethasone between the two test groups in a preclinical animal model over the duration of the study after 3 months aging at either refrigerated or stress storage conditions. The storage temperature did not affect either the duration or profile of release of dexamethasone from the OTX-DP.