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

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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 . https://doi.org/10.3390/pharmaceutics13040452

Title: Biopharmaceutics of Topical Ophthalmic Suspensions : Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin
Author: 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
Other contributor: University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Divisions of Faculty of Pharmacy
University of Helsinki, Division of Pharmaceutical Chemistry and Technology
University of Helsinki, Drug Research Program








Date: 2021-04
Language: eng
Number of pages: 13
Belongs to series: Pharmaceutics
ISSN: 1999-4923
DOI: https://doi.org/10.3390/pharmaceutics13040452
URI: http://hdl.handle.net/10138/330141
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.
Subject: ocular absorption
indomethacin
suspension
bioequivalence
dissolution
particle size
viscosity
QUANTITATIVE-EVALUATION
SYSTEMIC ABSORPTION
BIOAVAILABILITY
CORNEAL
PILOCARPINE
VEHICLES
RABBITS
IMPACT
317 Pharmacy
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