One-Year Stability of a Sustained Release Travoprost Biodegradable Hydrogel Punctum Plug for the Treatment of Glaucoma

Abstract

 

Purpose

 

To demonstrate the stability of the Sustained Release Travoprost Punctum Plug (OTX-TP) over a period of one-year at refrigerated storage conditions.

 

Methods

 

OTX-TP is comprised of travoprost encapsulated in polylactide microparticles that are entrapped within a dried biodegradable PEG hydrogel matrix and sized for insertion into the vertical canaliculus. Upon insertion the hydrogel swells to conform to the vertical canaliculus to ensure plug retention and release travoprost for a period of 3 months. The hydrogel is conjugated with fluorescein to aid plug visualization through the tissue using blue light from a slit lamp with a yellow filter. The foil packaged drug product was placed at refrigerated storage conditions consistent with ICH Q1A. Assay and travoprost related degradation products were determined following extraction and analysis by RP-HPLC. Product fluorescence was assessed when visualized through a tissue surrogate and a pass designation indicates easily seen when illuminated with a blue light and viewed through a yellow filter. The dried and hydrated product dimensions were measured using calibrated microscopy. Drug release rate was assessed in vitro in PBS at pH 7.4, incubated at 37°C through complete dissolution.

 

Results

 

The stability results are presented in Table One. The assay and dimensional values are listed as percentages relative to the time zero values demonstrating no appreciable change during storage. Results demonstrate insignificant changes in travoprost related degradation products. OTX-TP maintained its ability to be easily visualized through a tissue surrogate. The in vitro release results, plotted in Figure One, shows a consistent release profile following one-year refrigerated storage.

 

Conclusions

 

The results demonstrate the OTX-TP drug product stability following storage for one-year at refrigerated conditions. The sustained release of travoprost from the punctum plug during in vitro dissolution testing exhibits a near identical profile after one-year of refrigerated storage and this is important to ensure a consistent drug delivery rate to the eye for the potential treatment of glaucoma.