September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Enhancement of Ocular In-Situ Gelling Properties of Low Acyl Gellan Gum by Use of Ion Exchange
Author Affiliations & Notes
  • Amy Yan Li
    Belmont University College of Pharmacy, Nashville, Tennessee, United States
  • Britney Fink
    Belmont University College of Pharmacy, Nashville, Tennessee, United States
  • Tetchi Assamoi
    Belmont University College of Pharmacy, Nashville, Tennessee, United States
  • Kenneth W Reed
    Belmont University College of Pharmacy, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Amy Li, None; Britney Fink, None; Tetchi Assamoi, None; Kenneth Reed, Belmont University (P)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5046. doi:
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      Amy Yan Li, Britney Fink, Tetchi Assamoi, Kenneth W Reed; Enhancement of Ocular In-Situ Gelling Properties of Low Acyl Gellan Gum by Use of Ion Exchange. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5046.

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

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Abstract

Purpose : Timoptic XE® has demonstrated enhanced clinical effect for the active ingredient Timolol due to the ingredient low acyl (LA) Gellan. LA Gellan forms a gel in the presence of cations. Increased amounts of Timolol in the cornea, aqueous humor, and iris/ciliary body were achieved with increased formed gel strength. There are 217.5 monovalent ions to one divalent ion such as Ca+2 (more efficient gelation of LA Gellan) in the tear fluid. The purpose of this study was to determine if the addition of calcium gluconate to LA Gellan solution results in a stronger gel structure upon initial exposure to tear fluid due to the displacement of calcium from the gluconate ion by tear monovalent cations (Na+,K+).

Methods : Test solutions were measured at ambient temperature for pH and a viscosity sweep of 1-1,000 sec-1. It is assumed that a 40 µL drop of ophthalmic medication is added to 8 µL of tear volume to give an initial volume ratio of 5 to 1. Solutions of LA Gellan and LA Gellan-Calcium gluconate were mixed thoroughly with simulated tear fluid (STF) at a 5:1 ratio. The resulting gel was measured for viscosity at 34°-36° C. Each viscosity curve was modeled using the Ostwald-de-Waele viscosity model (larger k = larger viscosity) and Bingham yield value model curve fits. Thixotropic behavior was assessed by performing a viscosity sweep quickly followed by a low shear rate viscosity sweep (1-20 sec-1).

Results : LA Gellan mixed with STF resulted in higher viscosity and yield value gels when compared to other ingredient polymers believed to produce gel forming solutions. The addition of optimized amounts of calcium gluconate to LA Gellan formulations resulted in LA Gellan-Calcium Gluconate-STF gels (k=8.7-12.0 PaS) of higher strength than when LA Gellan alone was mixed with STF (k=3.8-4.6 PaS). Similarly, Alginate-Calcium Gluconate-STF (k= 25.3 PaS) gels were found to be of higher strength than Alginate-STF gels (k=0.2 PaS) alone. Formulations composed of LA Gellan with Zn2+ bound to a classic ion exchange resin (rather than Ca Gluconate) resulted in LA Gellan-Zn Resin-STF solutions (gels) with increased gel strength (k=9.6-14.3 PaS). Gellan experimental preparations demonstrated thixotropic behavior both before and after addition of STF.

Conclusions : It appears possible to enhance the initial in situ gel forming properties of LA Gellan by adding a divalent cation bound to an ion exchange molecule or resin.

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

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