Biopharmaceutics of Topical Ophthalmic Suspensions : Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin

Show simple item record Toropainen, Elisa Fraser-Miller, Sara J. Novakovic, Dunja Del Amo, Eva M. Vellonen, Kati-Sisko Ruponen, Marika Viitala, Tapani Korhonen, Ossi Auriola, Seppo Hellinen, Laura Reinisalo, Mika Tengvall, Unni Choi, Stephanie Absar, Mohammad Strachan, Clare Urtti, Arto 2021-05-20T12:19:02Z 2021-05-20T12:19:02Z 2021-04
dc.identifier.citation Toropainen , E , Fraser-Miller , S J , Novakovic , D , Del Amo , E M , Vellonen , K-S , Ruponen , M , Viitala , T , Korhonen , O , Auriola , S , Hellinen , L , Reinisalo , M , Tengvall , U , Choi , S , Absar , M , Strachan , C & Urtti , A 2021 , ' Biopharmaceutics of Topical Ophthalmic Suspensions : Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin ' , Pharmaceutics , vol. 13 , no. 4 , 452 .
dc.identifier.other PURE: 163791921
dc.identifier.other PURE UUID: 950d3574-849d-499f-bee5-845afe212462
dc.identifier.other WOS: 000643550500001
dc.identifier.other ORCID: /0000-0001-9074-9450/work/94195334
dc.identifier.other ORCID: /0000-0003-2058-2194/work/94196107
dc.description.abstract Eye drops of poorly soluble drugs are frequently formulated as suspensions. Bioavailability of suspended drug depends on the retention and dissolution of drug particles in the tear fluid, but these factors are still poorly understood. We investigated seven ocular indomethacin suspensions (experimental suspensions with two particle sizes and three viscosities, one commercial suspension) in physical and biological tests. The median particle size (d(50)) categories of the experimental suspensions were 0.37-1.33 and 3.12-3.50 mu m and their viscosity levels were 1.3, 7.0, and 15 mPa center dot s. Smaller particle size facilitated ocular absorption of indomethacin to the aqueous humor of albino rabbits. In aqueous humor the AUC values of indomethacin suspensions with different particle sizes, but equal viscosity, differed over a 1.5 to 2.3-fold range. Higher viscosity increased ocular absorption 3.4-4.3-fold for the suspensions with similar particle sizes. Overall, the bioavailability range for the suspensions was about 8-fold. Instillation of larger particles resulted in higher tear fluid AUC values of total indomethacin (suspended and dissolved) as compared to application of smaller particles. Despite these tear fluid AUC values of total indomethacin, instillation of the larger particles resulted in smaller AUC levels of indomethacin in the aqueous humor. This suggests that the small particles yielded higher concentrations of dissolved indomethacin in the tear fluid, thereby leading to improved ocular bioavailability. This new conclusion was supported by ocular pharmacokinetic modeling. Both particle size and viscosity have a significant impact on drug concentrations in the tear fluid and ocular drug bioavailability from topical suspensions. Viscosity and particle size are the key players in the complex interplay of drug retention and dissolution in the tear fluid, thereby defining ocular drug absorption and bioequivalence of ocular suspensions. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Pharmaceutics
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject ocular absorption
dc.subject indomethacin
dc.subject suspension
dc.subject bioequivalence
dc.subject dissolution
dc.subject particle size
dc.subject viscosity
dc.subject CORNEAL
dc.subject PILOCARPINE
dc.subject VEHICLES
dc.subject RABBITS
dc.subject IMPACT
dc.subject 317 Pharmacy
dc.title Biopharmaceutics of Topical Ophthalmic Suspensions : Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin en
dc.type Article
dc.contributor.organization Divisions of Faculty of Pharmacy
dc.contributor.organization Division of Pharmaceutical Chemistry and Technology
dc.contributor.organization Drug Research Program
dc.contributor.organization Division of Pharmaceutical Biosciences
dc.contributor.organization Pharmaceutical biophysics group
dc.contributor.organization Formulation and industrial pharmacy
dc.contributor.organization Clare Strachan / Research Group
dc.contributor.organization Drug Delivery
dc.contributor.organization Drug Delivery Unit
dc.description.reviewstatus Peer reviewed
dc.relation.issn 1999-4923
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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