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

Abstract

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 HC/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 13.6×10 −3 and 1.70×10 −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 6.73×10 −3 and 0.90×10 −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.