Considerations in the use of hydroxypropyl-β-cyclodextrin in the formulation of aqueous ophthalmic solutions of hydrocortisone

The in vivo ocular bioavailability of hydrocortisone (HC) in the NZW rabbit was determined following topical administration of solutions containing HC (1%) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) alone, or containing the mucoadhesive, viscosity enhancing polymers sodium hyaluronate (0.2 and 0.5% w/v) or Carbopol 934P (0.1% w/v). A 1% HC suspension was used as control. Formulation of HC as a solution with HP-beta-CD in the absence of polymer increased the bioavailability of HC in the aqueous humour by approximately 55% and cornea by 75% when compared to suspension. Inclusion of either polymer did not result in any further increase in ocular bioavailability over that noted for the polymer-free solution. The in vitro corneal permeability of HC was also evaluated. A linear relationship (r(2) = 0.999) was noted between corneal permeability and the concentration of free (uncomplexed) HC in solution. Permeability was greatest when formulated either as a suspension, or as an HP-beta-CD solution in which the concentration of free (uncomplexed) HC is equivalent to that of a saturated solution. Thus, when using cyclodextrins in the reformulation of ophthalmic suspensions as solutions, consideration must be given to the concentration of cyclodextrin used and to the benefits of including viscosity enhancing polymers. (C) 2000 Elsevier Science B.V. All rights reserved.