In Vitro / In Vivo Correlation of Travoprost Release from a Biodegradable Hydrogel Punctum Plug for the Treatment of Glaucoma

Abstract

 

Purpose

 

To demonstrate an in vitro / in vivo correlation (IVIVC) of sustained release travoprost from biodegradable hydrogel punctum plugs in an animal model compared to dissolution testing.

 

Methods

 

The Travoprost Punctum Plug (OTX-TP3) 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. Drug release rate from OTX-TP3 was assessed in vitro in PBS at pH 7.4, incubated at 37 C through complete dissolution and in vivo after subcutaneous implantation of two plugs in the scapular region of Sprague Dawley rats (n=40). Excision of 10 plugs from 5 rats per time point was performed and drug content per plug was determined via extraction and RP-HPLC.

 

Results

 

The daily in vitro and in vivo release of travoprost from OTX-TP3 was plotted over the duration of the studies (Figure One). Results demonstrate a sustained drug release relationship between the two studies and establish a 3-month drug release profile in an animal model correlating to conventional in vitro dissolution testing (Figure Two). For dose comparison purposes the daily amount of travoprost administered in a Travatan Z eye drop (from Travatan Z NDA #21-994) is presented in Figure One.

 

Conclusions

 

The in vivo release results show good agreement with standard in vitro dissolution testing and demonstrate a suitable model for the development of an IVIVC. Sustained release of travoprost from biodegradable plugs can deliver travoprost for a period of 3 months in an in vivo animal model that meets or exceeds the daily dose from eye drops.

 

 

 

Keywords: 503 drug toxicity/drug effects • 607 nanotechnology • 633 outflow: trabecular meshwork