March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Corticosteroid Delivery from a Punctum Plug in a Canine Model Over 21-Days
Author Affiliations & Notes
  • Ankita Desai
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Michael Bassett
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Art Driscoll
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Peter Jarrett
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Amar Sawhney
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Leslie Jost
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Abbe Miller
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Charles Blizzard
    R & D, Ocular Therapeutix, Inc., Bedford, Massachusetts
  • Footnotes
    Commercial Relationships  Ankita Desai, Ocular Therapeutix, Inc. (E); Michael Bassett, Ocular Therapeutix, Inc. (E); Art Driscoll, Ocular Therapeutix, Inc. (E); Peter Jarrett, Ocular Therapeutix, Inc. (E); Amar Sawhney, Ocular Therapeutix, Inc. (E); Leslie Jost, Ocular Therapeutix, Inc. (E); Abbe Miller, Ocular Thjerapeutix, Inc. (E); Charles Blizzard, Ocular Therapeutix, Inc. (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 460. doi:
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    • Get Citation

      Ankita Desai, Michael Bassett, Art Driscoll, Peter Jarrett, Amar Sawhney, Leslie Jost, Abbe Miller, Charles Blizzard; Corticosteroid Delivery from a Punctum Plug in a Canine Model Over 21-Days. Invest. Ophthalmol. Vis. Sci. 2012;53(14):460.

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

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Abstract
 
Purpose:
 

To examine the influence of aqueous solubility on the in vivo release rate of three corticosteroids from a hydrogel punctum plug in a canine model.

 
Methods:
 

Micronized prednisolone (Pred), prednisolone acetate (PA) and dexamethasone (Dex) having a water solubility of 223, 89 and 17 µg/mL, respectively were suspended in a multi-arm PEG solution and injected into small bore tubing prior to cross-linking. The steroid in hydrogel matrix was subsequently dried and cut into punctum plugs. The plugs were inserted into the inferior canaliculus of beagles and a subset was removed each week for photographic imaging and to analyze drug content following extraction. Percent drug release was plotted over time relative to content prior to insertion.

 
Results:
 

As shown in Figure 1, the steroids release in vivo from the plug at a rate relative to their aqueous solubility. The most soluble Pred is > 95% released in 14 days, whereas the lesser soluble Dex and PA has released 54 and 41%, respectively over 21 days. Images of a steroid loaded plug demonstrating weekly drug release are seen in the bottom of Figure 1.

 
Conclusions:
 

Topical corticosteroids, such as Dex, Pred and PA are used to treat inflammation in a variety of ophthalmic conditions. Many therapies require multiple daily administrations (hourly for severe conditions) for a prolonged period making a single dose therapy a more convenient option that may help ensure patient compliance and better provide necessary treatment. Aside from drug potency and ocular penetration, aqueous solubility must be considered when developing an ophthalmic sustained drug delivery system, as it can greatly influence the in vivo release rate as demonstrated in the canine model. A more water soluble drug may be preferred if short term therapy is required, whereas a less soluble drug may be preferred if long term therapy is needed.  

 
Keywords: drug toxicity/drug effects • inflammation • corticosteroids 
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