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dc.contributor.authorLoftsson, Thorsteinn
dc.contributor.authorJansook, Phatsawee
dc.contributor.authorStefánsson, Einar
dc.date.accessioned2013-09-02T11:00:53Z
dc.date.available2013-09-02T11:00:53Z
dc.date.issued2012-11
dc.date.submitted2013-09-02
dc.identifier.citationActa Ophthalmol 2012, 90(7):603-8en_GB
dc.identifier.issn1755-3768
dc.identifier.pmid22269010
dc.identifier.doi10.1111/j.1755-3768.2011.02299.x
dc.identifier.urihttp://hdl.handle.net/2336/300647
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en_GB
dc.description.abstractTopically applied carbonic anhydrase inhibitors (CAIs) in eye drop solutions are commonly used to treat glaucoma. However, local eye irritation and multiple daily administrations may hamper their clinical usefulness. Aqueous eye drop formulations that improve their topical bioavailability and reduce their eye irritation can improve their clinical efficacy. Earlier studies showed that dorzolamide and closely related CAIs are more effectively delivered into the eye from acidic eye drop solutions than from comparable neutral solutions. Consequently, dorzolamide was marketed as an aqueous pH 5.6 eye drop solution (Trusopt(®) , Merck). Later, it was shown that increasing the pH of the eye drops from pH 5.6 to physiologic pH significantly reduced their local irritation. Earlier attempts to use cyclodextrins (CDs) as ocular penetration enhancers in dorzolamide eye drop solutions failed since; although the CDs were able to enhance the aqueous solubility of dorzolamide, increasing the pH from 5.6 to physiologic pH reduced the ability of the drug to permeate into the eye. Later, it was discovered that formulating the drug as aqueous dorzolamide/γCD eye drop microparticle suspension resulted in significant bioavailability enhancement. The solid dorzolamide/γCD microparticles are mucoadhesive and release dorzolamide into the aqueous tear fluid for extended time period. Consequently, sustained high dorzolamide concentrations in aqueous humour and various eye tissues were observed after single administration of the aqueous dorzolamide/γCD eye drop microsuspension. The microsuspension has a potential of being developed into a once-a-day eye drop product. This article reviews the physicochemical properties of dorzolamide, its permeation characteristics and topical bioavailability.
dc.language.isoenen
dc.publisherWiley-Blackwellen_GB
dc.relation.urlhttp://dx.doi.org/10.1111/j.1755-3768.2011.02299.xen_GB
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1111/j.1755-3768.2011.02299.x/pdfen_GB
dc.rightsArchived with thanks to Acta ophthalmologicaen_GB
dc.subject.meshAdministration, Topicalen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAntihypertensive Agentsen_GB
dc.subject.meshAqueous Humoren_GB
dc.subject.meshBiological Availabilityen_GB
dc.subject.meshCarbonic Anhydrase Inhibitorsen_GB
dc.subject.meshDrug Delivery Systemsen_GB
dc.subject.meshGlaucomaen_GB
dc.subject.meshHumansen_GB
dc.subject.meshOphthalmic Solutionsen_GB
dc.subject.meshSulfonamidesen_GB
dc.subject.meshThiophenesen_GB
dc.titleTopical drug delivery to the eye: dorzolamide.en
dc.typeArticleen
dc.contributor.departmentFaculty of Pharmaceutical Sciences, University of Iceland, Reykjavik, Iceland.en_GB
dc.identifier.journalActa ophthalmologicaen_GB
dc.rights.accessNational Consortium - Landsaðganguren
html.description.abstractTopically applied carbonic anhydrase inhibitors (CAIs) in eye drop solutions are commonly used to treat glaucoma. However, local eye irritation and multiple daily administrations may hamper their clinical usefulness. Aqueous eye drop formulations that improve their topical bioavailability and reduce their eye irritation can improve their clinical efficacy. Earlier studies showed that dorzolamide and closely related CAIs are more effectively delivered into the eye from acidic eye drop solutions than from comparable neutral solutions. Consequently, dorzolamide was marketed as an aqueous pH 5.6 eye drop solution (Trusopt(®) , Merck). Later, it was shown that increasing the pH of the eye drops from pH 5.6 to physiologic pH significantly reduced their local irritation. Earlier attempts to use cyclodextrins (CDs) as ocular penetration enhancers in dorzolamide eye drop solutions failed since; although the CDs were able to enhance the aqueous solubility of dorzolamide, increasing the pH from 5.6 to physiologic pH reduced the ability of the drug to permeate into the eye. Later, it was discovered that formulating the drug as aqueous dorzolamide/γCD eye drop microparticle suspension resulted in significant bioavailability enhancement. The solid dorzolamide/γCD microparticles are mucoadhesive and release dorzolamide into the aqueous tear fluid for extended time period. Consequently, sustained high dorzolamide concentrations in aqueous humour and various eye tissues were observed after single administration of the aqueous dorzolamide/γCD eye drop microsuspension. The microsuspension has a potential of being developed into a once-a-day eye drop product. This article reviews the physicochemical properties of dorzolamide, its permeation characteristics and topical bioavailability.


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