July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
A Highly Bioavailable Nanocore (OcuSurf™) Brinzolamide Drug Product for Glaucoma Therapy, Compared to Azopt™
Author Affiliations & Notes
  • Koushik Barman
    Pharmaceutical Development, Integral BioSystems, Bedford, Massachusetts, United States
  • Kevin Ward
    Pharmaceutical Development, Integral BioSystems, Bedford, Massachusetts, United States
  • Chinghong Li
    Pharmaceutical Development, Integral BioSystems, Bedford, Massachusetts, United States
  • Shikha P Barman
    Pharmaceutical Development, Integral BioSystems, Bedford, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Koushik Barman, Integral BioSystems (E), Integral BioSystems (P); Kevin Ward, Integral BioSystems (E), Integral BioSystems (P); Chinghong Li, Integral BioSystems (E); Shikha Barman, Integral BioSystems (E), Integral BioSystems (P)
  • Footnotes
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Investigative Ophthalmology & Visual Science July 2018, Vol.59, 5690. doi:https://doi.org/
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      Koushik Barman, Kevin Ward, Chinghong Li, Shikha P Barman; A Highly Bioavailable Nanocore (OcuSurf™) Brinzolamide Drug Product for Glaucoma Therapy, Compared to Azopt™. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5690. doi: https://doi.org/.

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

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Abstract

Purpose : Glaucoma is a chronic ocular disorder that is characterized by high intraocular pressure (IOP) and is one of leading causes of blindness globally. Characterized by IOP, one of the treatments for glaucoma is Brinzolamide, a specific, non-competitive, reversible and effective inhibitor of carbonic anhydrase II (CA-II) and is able to suppress the formation of aqueous humor. Brinzolamide 1% ophthalmic suspension is a commercialized glaucoma medication with relatively few adverse events; it can be used as a first line medication, as well as an adjunct to other therapies to manage chronic glaucoma. We hypothesized that the delivery of Brinzolamide can be improved. For drug suspensions to absorb, they would need to dissolve first. In the ocular space, rapid fluid turnover and loss via the naso-lacrimal duct results in just 5% of the drug being absorbed. We have invented a mucosa-interactive, biphasic delivery system, OcuSurf-BZ (OS-BZ), which contains dissolved Brinzolamide and is nano-engineered to rapidly permeate the cornea, potentially requiring less drug to generate a therapeutic response. We present the comparative physicochemical, ex-vivo and in-vivo characterization of commercial Brinzolamide, 1% suspension and OS-BZ, 1% to test this hypothesis of enhanced bioavailability.

Methods : Physicochemical characterization methods were particle size determination, viscosity, in-vitro release and ex-vivo corneal permeability. Permeability studies were performed through freshly excised corneal membranes, using diffusion cells and permeated drug quantitated by LC/MS. In-vivo pharmacokinetic studies were performed in a rabbit model; tear fluid was collected and analyzed by LC/MS/MS. Irritation assessment of the OS-BZ cohort was performed in-vivo, using a Draize grading scale.

Results : Particle size of OS-BZ was d50<200 nm, compared to a d50 of 2.5 microns for commercial Brinzolamide. High permeation rates of the drug were observed in the OS-BZ cohort, in both in-vivo and in-vitro studies plausibly due to presence of dissolved drug. In contrast, drug permeation rate were many-fold lower in the commercial Brinzolamide group. OS-BZ eye-drops were well tolerated in rabbit eye, with twice-daily dosing over 3 days.

Conclusions : The OS–BZ product shows enhanced release rates compared to the commercial product demonstrating an enhanced bioavailability of Brinzolamide via this novel delivery modality.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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