June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Physicochemical characterization of Tobradex and Tobradex ST under physiological conditions
Author Affiliations & Notes
  • Stephanie Choi
    Food and Drug Administration, Silver Spring, Maryland, United States
  • Peter Petrochenko
    Food and Drug Administration, Silver Spring, Maryland, United States
  • Yong Wu
    Food and Drug Administration, Silver Spring, Maryland, United States
  • Darby Kozak
    Food and Drug Administration, Silver Spring, Maryland, United States
  • Jiwen Zheng
    Food and Drug Administration, Silver Spring, Maryland, United States
  • Footnotes
    Commercial Relationships   Stephanie Choi, None; Peter Petrochenko, None; Yong Wu, None; Darby Kozak, None; Jiwen Zheng, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4459. doi:
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      Stephanie Choi, Peter Petrochenko, Yong Wu, Darby Kozak, Jiwen Zheng; Physicochemical characterization of Tobradex and Tobradex ST under physiological conditions
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):4459.

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

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Abstract

Purpose : pH responsive viscosity modulation of ophthalmic suspensions using polysaccharides may improve drug availability in the eye by retaining the suspended particulates for longer times, but creates complexity for robust physicochemical characterization of generic analogues. We tested Tobradex and Tobradex ST using different polysaccharide viscosity modifiers at physiological conditions in a dynamic setting with simulated tear fluid and characterized their respective particle size distributions to determine the effect of pH on their physicochemical properties.

Methods : Simulated tear fluid and phosphate buffered saline were prepared and used as dispersants for viscosity and size measurements. Dispersants were buffered to simulate the pH of the eye. A cone-and-plate geometry was used to obtain full rheological profiles of the drug formulations at different dilutions, pH values, and shear rates. Particle size measurement was performed at both sink and non-sink conditions using light scattering and diffraction instruments to evaluate changes in particle size upon dilution. Optical and electron microscopy was performed to confirm results and evaluate particle morphology.

Results : Formulations containing hydroxyethyl cellulose retained a Newtonian viscosity and overall viscosity decreased when diluted with aqueous dispersants. Xanthan gum imparted a much higher stock viscosity by weight along with a clearly detectable shear thinning response of the stock solution. When the product containing xanthan gum came in contact with tear fluid (pH 7.4), the viscosity increased over 5 times (at 1:2 parts dilution with tear fluid). Different particle sizing methods and sample preparation methods yielded varying results for particle size of both formulations. Diluted suspensions were susceptible to a gradual decrease in size during measurements. Microscopy confirmed particle sizing results and revealed morphological differences.

Conclusions : Xanthan gum was theorized to form a bond with tobramycin, possibly reducing bulk viscosity to a lower value than an equivalent aqueous solution of xanthan gum, an effect that was reversed upon dilution and a change in pH. An additional consequence of dilution is a decrease in particle size which requires modification of sizing technique and dispersant.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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