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 and Additional Polymers
Author Affiliations & Notes
  • Kenneth W Reed
    Pharmaceutical Sciences, Belmont University, Nashville, Tennessee, United States
  • Amy Li
    Pharmaceutical Sciences, Belmont University, Nashville, Tennessee, United States
  • Britney Fink
    Pharmaceutical Sciences, Belmont University, Nashville, Tennessee, United States
  • Tetchi Assamoi
    Pharmaceutical Sciences, Belmont University, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Kenneth Reed, Belmont University (P); Amy Li, None; Britney Fink, None; Tetchi Assamoi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5045. doi:
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      Kenneth W Reed, Amy Li, Britney Fink, Tetchi Assamoi; Enhancement of Ocular In-Situ Gelling Properties of Low Acyl Gellan Gum by Use of Ion Exchange and Additional Polymers. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5045.

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

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Abstract

Purpose : Low acyl (LA) Gellan has been successfully used as an ingredient to form ocular in situ gelling solutions (GFS) due to its property of increasing in viscosity when exposed to tear film cations. Previous experimental work indicates that the addition of divalent cations bound to ion exchange molecules may be added to LA Gellan to increase gel strength when initially exposed to tear film. The purpose of this investigation was to determine if the addition of alternate polymers to LA Gellan results in stronger gels than LA-Gellan alone.

Methods : Final test preparations were measured at ambient temperature for pH and viscosity (1-1,000 sec-1). Experimental preparations were mixed thoroughly with simulated tear fluid (STF) at a 5:1 ratio. The final solution (gel) was measured (34°-36° C) for viscosity. Each viscosity curve was modeled using the Ostwald-de-Waele (viscosity model) and Bingham (yield value) curve fits. Thixotropic behavior was assessed by performing a high shear rate viscosity sweep (1-1000 sec-1) quickly followed by a low shear rate viscosity sweep (1-20 sec-1).
Various 0.68% timolol Maleate compositions were prepared and one g of each Timolol preparation was placed inside dialysis tubing (MWCO = 3,500-5,000). The dialysis “bag” was then transferred into 100 mL of receiving fluid. Timed samples of the receiving fluid were assayed for Timolol concentration using UV analysis.

Results : Polymers with vinyl pyrrolidone groups (PVP) were found to be effective in improving the initial gel strength of LA Gellan-Ca Gluconate solutions. Timolol release was found to be significantly slowed when formulated in a LA Gellan-Ca Gluconate-PVP formulation. It was discovered that a mixture of high acyl (HA) and LA Gellan in solution results in a stronger initial gel than when LA Gellan alone was used, especially if Ca Gluconate is present at the optimal amount. Additionally, the HA and LA combination gels resist being dissolved by STF even in the presence of relatively large quantities of STF.

Conclusions : Select polymers can be added to LA Gellan-Ca Gluconate solutions to produce GFS preparations that when compared to LA Gellan-Ca Gluconate alone: (1) form stronger initial gels upon addition to the tear fluid, (2) slow the diffusion of drug from the formed gel, and (3) resists dissolution of the formed gel by tears.

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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