Modified β-Cyclodextrin (SBE7-β-CyD) with Viscous Vehicle Improves the Ocular Delivery and Tolerability of Pilocarpine Prodrug in Rabbits

The complexation of pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, with various β-cyclodextrin (β-CyD) derivatives was studied by the phase solubility method. The effects of coadministered sulphobutyl ether β-CyD (SBE7-β-CyD) with and without poly(vinyl alcohol) (PVA) on the miotic response and eye irritation of the prodrug were investigated in pigmented rabbits. The pilocarpine prodrug formed 1:1 inclusion complexes with variably substituted sulphobutyl ether derivatives of β-CyD (SBE4-β-CyD and SBE7-β-CyD), and 1:1 and 1:2 complexes with hydroxypropyl-β-CyD (HP-β-CyD) at pH 7:4. Coadministered SBE7-β-CyD eliminated the eye irritation due to the pilocarpine prodrug, but also decreased the miotic response. Ocular absorption of the prodrug was improved by increasing the viscosity of prodrug/SBE7-β-CyD solution with PVA without inducing any eye irritation. Eye irritation due to viscous prodrug/SBE7-β-CyD solutions was comparable with isotonic NaCl solution. We conclude that administration of pilocarpine prodrug in viscous SBE7-β-CyD solution decreases substantially eye irritation while ocular absorption is not affected.