Permeability of a soft steroid, loteprednol etabonate, through an excised rabbit cornea.
The objective of this work was to study the in vitro permeability characteristics of a "soft" steroid, loteprednol etabonate 1 in different vehicles across excised rabbit cornea using a transcorneal permeation system. The vehicles studies were aqueous solutions of beta-cyclodextrin derivatives; 2-hydroxypropyl beta-cyclodextrin (HPCD) and heptakis (2,6-di-O-methyl) beta-cyclodextrin (DMCD); and DMCD together with 5 and 10% propylene glycol (PG) or dimethyl sulfoxide (DMSO). Two experimental suspension products of the steroid, 0.1% and 0.5%, and the suspensions of the steroid in commercial lubricant ophthalmic solutions which include Liquifilm Tears and Tears Plus were also studied for their possible use as vehicles to deliver the steroid across the cornea. The observed permeability rate of the soft steroid from DMCD was found to be 13-fold greater than from HPCD. The presence of varying percentages of PG and DMSO with DMCD decreased the flux of the steroid. Transcorneal permeability of the steroid was found to be insignificant from aqueous buffer (pH 7.4) and commercial lubricant ophthalmic solutions. The flux of the steroid in 20% DMCD (23 micrograms/hr/cm2) was found to be comparable with 0.5% commercial suspension (20.5 micrograms/hr/cm2). The barrier function of corneal epithelium for the steroid in 0.5% experimental suspension was also investigated. When the corneal epithelium was removed, the lag time of the lipophilic soft steroid decreased but the flux value did not change.
Reddy
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IK
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy and Health Sciences, Northeast Louisiana University, Monroe, USA.
Khan
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MA
Wu
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WM
Bodor
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NS
D000287:Administration, Topical; D000730:Androstadienes / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D000069559:Loteprednol Etabonate; D008297:Male; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D019946:Propylene Glycol; D011409:Propylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D011409:Propylene Glycols; D019946:Propylene Glycol; D000069559:Loteprednol Etabonate; D004121:Dimethyl Sulfoxide