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  • Title: In vitro transcorneal permeation of ketorolac tromethamine from buffered and unbuffered aqueous ocular drops.
    Author: Malhotra M, Majumdar DK.
    Journal: Indian J Exp Biol; 1997 Sep; 35(9):941-7. PubMed ID: 9475074.
    Abstract:
    In vitro transcorneal permeation of ketorolac tromethamine from 0.5% w/v solutions containing equimolar (0.02 M) concentrations of citrate (pH 6.5), phosphate (pH 6.5 and 7), citrate-phosphate (pH 7) and borate (pH 7) buffers was studied using goat cornea. Cumulative % permeation was maximum with phosphate buffered drops of pH 6.5. The effect of pH and ionic strength on permeation of ketorolac tromethamine from buffered (phosphate) drops was next investigated. Cumulative % permeation of ketorolac tromethamine from buffered drops was pH dependent being maximum at pH 4.5. Adjustment of ionic strength of drops to 0.2 resulted in decreased permeation of drug. Permeation of ketorolac tromethamine from unbuffered drops of varying pH and ionic strength 0.2 was also pH dependent and was maximum at pH 4.5. Buffered drops of pH between 4.5-5.5, ionic strength 0.2, provided better permeation of drug compared to unbuffered drops of same pH and ionic strength. Above pH 6.5 unbuffered drops showed better permeation than buffered drops. Increase in molarity of phosphate buffer (pH 4.5) used in making drops, between 0 to 0.15 M increased permeation. Aqueous drops of ketorolac tromethamine formulated in 0.15 M phosphate buffer of pH 4.5 and ionic strength 0.2 showed maximum cumulative % permeation in vitro. Considering lacrimation induced drug loss in vivo, by buffer of high concentration, ketorolac tromethamine drops formulated in buffer of low molarity, pH 4.5 and ionic strength 0.2 appear suitable.
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