September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Dexamethasone Degradation During In Vitro Release from an Intravitreal Implant
Author Affiliations & Notes
  • Brock Matter
    Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, United States
  • Alireza Ghaffari
    Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, United States
  • David Bourne
    Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, United States
  • Yan Wang
    Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, United States
  • Stephanie Choi
    Center for Drug Evaluation and Research, FDA, Silver Spring, Maryland, United States
  • Uday B Kompella
    Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, United States
  • Footnotes
    Commercial Relationships   Brock Matter, None; Alireza Ghaffari, None; David Bourne, None; Yan Wang, None; Stephanie Choi, None; Uday Kompella, None
  • Footnotes
    Support  FDA Grant 1U01FD004929
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4010. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Brock Matter, Alireza Ghaffari, David Bourne, Yan Wang, Stephanie Choi, Uday B Kompella; Dexamethasone Degradation During In Vitro Release from an Intravitreal Implant
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):4010.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : It has been observed that dexamethasone undergoes degradation after it is released from implants into the aqueous medium during in vitro release testing. In order to obtain correct in vitro release profile, degradation of dexamethasone needs to be properly monitored and measured. The purpose of this study was to develop an LC-MS/MS method to monitor and measure major degradation products of dexamethasone in aqueous medium using both plain dexamethasone solution and release samples obtained from dexamethasone-loaded implants.

Methods : Dexamethasone and dexamethasone-loaded implants made using poly(lactide-co-glycolide) were incubated in PBS buffer (pH 7.4) at 37 and 45 oC, with or without light exposure. Plain dexamethasone solution was also incubated at room temperature. Samples were collected over several days, spiked with d4-dexamethasone as internal standard, and the concentrations of dexamethasone and thirteen dexamethasone degradation products were analyzed using a triple stage quadrupole mass spectrometer.

Results : The mass spectrometer was operated in multiple reaction monitoring mode set to look for the product ions that resulted from the characteristic loss of fluorine from each precursor ion. Using this method, we could detect dexamethasone degradation products in the incubation medium for the implants as well as plain drug. The extent of degradation increased with the study duration as well as light exposure and elevation of temperature. Dexamethasone incubated in PBS buffer at 37°C, exposed to ambient light was found to have a half-life of about 10 days, while dexamethasone at 45°C in the absence of light had a half-life of about 7 days. A mathematical model was developed to estimate drug release after accounting for drug degradation.

Conclusions : Dexamethasone, when incubated in aqueous media, produces degradation products in a time, temperature, and light exposure dependent manner. Degradation products were also detected in the in vitro release samples obtained from dexamethasone-loaded PLGA implants. The analytical method developed for monitoring dexamethasone degradation products can potentially be used for assessing the stability of dexamethasone during manufacturing, storage, and use of various dosage forms.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×