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Dexamethasone delivery to posterior segment of the eye

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Abstract

Due to anatomic barriers and lacrimal drainage it is difficult to obtain therapeutic drug concentrations in the posterior part of the eye after topical drug administrations. Lipophilic cyclodextrins, such as randomly methylated β-cyclodextrin (RMβCD), are known to act both as solubilizers of water-insoluble drugs in aqueous solutions and as penetration enhancers that reduce the barrier function of lipophilic membranes. The purpose of this study was to investigate the effects of RMβCD on dexamethasone delivery from aqueous eye drop solution into rabbit eyes. Dexamethasone (0.5 and 1.5% w/v) drops (50 μl) were administered to the left eye of rabbits (n = 6) and the drug levels measured in different eye tissues 2 h after administration. In aqueous humor dexamethasone levels were 1,190 ± 110 and 1,670 ± 630 ng/g (mean ± SD) after administration of the 0.5 and 1.5% dexamethasone eye drops, respectively. In the retina the levels were 33 ± 7 and 66 ± 49 ng/g, and in optic nerve 41 ± 12 and 130 ± 50 ng/g, respectively. In a previous study the dexamethasone concentration in aqueous humor after topical administration of 1.3% (w/v) dexamethasone eye drops in aqueous 2-hydroxypropyl-β-cyclodextrin (HPβCD) solution was determined to be 320 ± 230 ng/g and 66 ± 20 ng/g after administration of Maxidex® eye drops. Both the hydrophilic HPβCD and the lipophilic RMβCD enhance topical dexamethasone delivery into the eye, but of the two, the lipophilic RMβCD results in higher dexamethasone concentrations.

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References

  1. Ahmed, I., Gokhale, R.D., Shah, M.V., Patton, T.F.: Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea. J. Pharm. Sci. 76, 583–586 (1987)

    Article  CAS  Google Scholar 

  2. Wang, W., Sasaki, H., Chien, D.-S., Lee, V.H.L.: Lipophilicity influence on conjunctival drug penetration in the pigmented rabbit: a comparison with corneal penetration. Curr. Eye Res. 10, 571–579 (1991)

    CAS  Google Scholar 

  3. Loftsson, T., Stefánsson, E.: Effect of cyclodextrins on topical drug delivery to the eye. Drug Devel. Ind. Pharm. 23, 473–481 (1997)

    Article  CAS  Google Scholar 

  4. Loftsson, T., Stefánsson, E.: Cyclodextrins in eye drop formulations: enhanced topical delivery of corticosteroids to the eye. Acta Ophthalmol. Scand. 80, 144–150 (2002)

    Article  CAS  Google Scholar 

  5. Chrai, S.S., Patton, T.F., Mehta, A., Robinson, J.R.: Lacrimal and instilled fluid dynamics in rabbit eye. J. Pharm. Sci. 62, 1112–1121 (1973)

    Article  CAS  Google Scholar 

  6. Gangrade, N.K., Gaddipati, N.B., Ganesan, M.G., Reddy, I.K.: Topical ophthalmic formulations: basic considerations. In: Reddy, I.K. (ed.) Ocular Therapeutics and Drug Delivery, pp. 377–403. Technomic Publications, Lancaster (1996)

    Google Scholar 

  7. Loftsson, T., Järvinen, T.: Cyclodextrins in ophthalmic drug delivery. Adv. Drug Deliv. Rev. 36, 59–79 (1999)

    Article  Google Scholar 

  8. Washington, N., Washington, C., Wilson, C.G.: Ocular drug delivery. Physiological pharmaceutics: barriers to drug absorption, pp. 249–270. Taylor and Francis, London (2001)

  9. Myles, M.E., Neumann, D.M., Hill, J.M.: Recent progress in ocular drug delivery for posterior segment disease: emphasis on transsclera iontophoresis. Adv. Drug Deliv. Rev. 57, 2063–2079 (2005)

    Article  CAS  Google Scholar 

  10. Raghava, S., Hammond, M., Kompella, U.B.: Periocular routes for retinal drug delivery. Exp. Opin. Drug Deliv. 1, 99–114 (2004)

    Article  Google Scholar 

  11. Yasukawa, T., Ogura, Y., Sakurai, E., Tabata, Y., Kimura, H.: Intraocular sustained drug delivery using implantable polymer devices. Adv. Drug Deliv. Rev. 57, 2033–2047 (2005)

    Article  CAS  Google Scholar 

  12. Jonas, J.B.: Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and neovascular diseases. Acta Ophthalmol. Scand. 83, 645–663 (2005)

    Article  Google Scholar 

  13. Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, P.J.: Experimental and computatorial approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3–26 (2001)

    Article  CAS  Google Scholar 

  14. Amidon, G.L., Lennernäs, H., Shah, V.P., Crison, J.R.: A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12, 413–420 (1995)

    Article  CAS  Google Scholar 

  15. Loftsson, T., Masson, M.: Cyclodextrins in topical drug formulations: theory and practice. Int. J. Pharm. 225, 15–30 (2001)

    Article  CAS  Google Scholar 

  16. Sinha, V.R., Bindra, S., Kumria, R., Nanda, A.: Cyclodextrin as skin-penetration enhancers. Pharm. Technol. 27(3), 120–138 (2003)

    CAS  Google Scholar 

  17. Loftsson, T., Konráǒsdóttir, F., Másson, M.: Influence of aqueous diffusion layer on passive drug diffusion from aqueous cyclodextrin solutions through biological membranes. Pharmazie 61, 83–89 (2006)

    CAS  Google Scholar 

  18. Loftsson, T., Sigfússon, S.D., Sigurðsson, H.H., Másson, M.: The effects of cyclodextrins on topical delivery of hydrocortisone: the aqueous diffusion layer. S.T.P. Pharma Sci. 13, 125–131 (2003)

    CAS  Google Scholar 

  19. Merkus, F.W.H.M., Verhoef, J.C., Marttin, E., Romeijn, S.G., van der Kuy, P.H.M., Hermens, W.A.J.J., Schipper, N.G.M.: Cyclodextrin in nasal drug delivery. Adv. Drug Deliv. Rev. 36, 41–57 (1999)

    Article  CAS  Google Scholar 

  20. Yang, T., Hussain, A., Paulson, J., Abbruscato, T.J., Ahsan, F.: Cyclodextrins in nasal delivery of low-molecular-weight heparins: in vivo and in vitro studies. Pharm. Res. 21, 1127–1136 (2004)

    Article  CAS  Google Scholar 

  21. Loftsson, T., Fridriksdottir, H., Thorisdottir, S., Stefansson, E.: The effect of hydroxypropyl methylcellulose on release of dexamethasone from aqueous 2-hydroxypropyl-β-cyclodextrin formulations. Int. J. Pharm. 104:181–184 (1994)

    Article  CAS  Google Scholar 

  22. Loftsson, T., Hreinsdóttir, D., Másson, M.: Evaluation of cyclodextrin solubilization of drugs. Int. J. Pharm. 302, 18–28 (2005)

    Article  CAS  Google Scholar 

  23. Higuchi, T., Connors, K.A.: Phase-solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)

    CAS  Google Scholar 

  24. Weijtens, O., Feron, E.J., Schoemaker, R.C., Cohen, A.F., Lentjes, E.G.W.M., Romijn, F.P.H.T.M., van Meurs, J.C.: High concentration of dexamethasone in aqueous and vitreous after subconjunctival injection. Am. J. Ophthalmol. 128, 192–197 (1999)

    Article  CAS  Google Scholar 

  25. Shiah, J.-G., Bhagat, R., Nivaggioli, T., Peng, L., Chou, D., Weber, D.A.: Ocular implant made by a double extrusion process. US Patent Application No.: 2005/0048099, Allergan Inc. 3 March 2005, USA

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Acknowledgement

This work was supported by a grant from the Icelandic Centre for Research.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Iceland, Hofsvallagata 53, 107, Reykjavik, Iceland

    Thorsteinn Loftsson, Hákon H. Sigurdsson, Dagný Hreinsdóttir & Fífa Konrádsdóttir

  2. Department of Ophthalmology, University Hospital-Landspitalinn, 101, Reykjavik, Iceland

    Einar Stefánsson

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  1. Thorsteinn Loftsson
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  2. Hákon H. Sigurdsson
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  3. Dagný Hreinsdóttir
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  4. Fífa Konrádsdóttir
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  5. Einar Stefánsson
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Correspondence to Thorsteinn Loftsson.

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Loftsson, T., Sigurdsson, H.H., Hreinsdóttir, D. et al. Dexamethasone delivery to posterior segment of the eye. J Incl Phenom Macrocycl Chem 57, 585–589 (2007). https://doi.org/10.1007/s10847-006-9253-4

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  • DOI: https://doi.org/10.1007/s10847-006-9253-4

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