Evaluation of a hydrocortisone/hydroxypropyl-β-cyclodextrin solution for ocular drug delivery

The effect of hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility and chemical stability of hydrocortisone (HC) was investigated with an ultimate aim of formulating a stable topical ophthalmic solution of HC. The ocular bioavailability following topical administration to rabbits of the aqueous formulation of HC was then compared to that of a suspension formulation having an equivalent HC concentration. The aqueous solubility of HC was markedly increased upon addition of HP-β-CD due the formation of a soluble 1:1 inclusion complex. The apparent association constant of the HP-β-CD complex determined by phase-solubility analysis was estimated to be 0.636 mM^-1. The decomposition of HC in pH 7.4 phosphate buffer followed pseudo first-order kinetics having rate constants of 13.6 x 10^-3 and 1.70 x 10^-3 h^-1, respectively, in the presence and absence of disodium edetate. Complexation with HP-β-CD increased the chemical stability of HC with the respective pseudo first-order rate constants of decomposition being reduced to 6.73 x 10^-3 and 0.90 x 10^-3 h^-1. The ocular bioavailability following topical administration to rabbits of a tritium labelled 1% HC solution formulation of the HC/HP-β-CD complex was lower than that of a 1% suspension formulation. A significant reduction (p < 0.05) of between 25 and 40% was apparent in the cornea, aqueous humour, iris and sclera.