MODIFIED BETA-CYCLODEXTRIN (SBE7-BETA-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-xylylen e) bispilocarpate, with various beta-cyclodextrin (beta-CyD) derivativ es was studied by the phase solubility method. The effects of coadmini stered sulphobutyl ether beta-CyD (SBE7-beta-CyD) with and without pol y(vinyl alcohol) (PVA) on the miotic response and eye irritation of th e prodrug were investigated in pigmented rabbits. The pilocarpine prod rug formed 1:1 inclusion complexes with variably substituted sulphobut yl ether derivatives of beta-CyD (SBE4-beta-CyD and SBE7-beta-CyD), an d. 1:1 and 1:2 complexes with hydroxypropyl-beta-CyD (HP-beta-CYD) at pH 7.4. Coadministered SBE7-beta-CyD eliminated the eye irritation due to the pilocarpine prodrug, but also decreased the miotic response. O cular absorption of the prodrug was improved by increasing the viscosi ty of prodrug/SBE7-beta-CyD solution with PVA without inducing any eye irritation. Eye irritation due to viscous prodrug/SBE7-beta-CyD solut ions was comparable with isotonic NaCl solution. We conclude that admi nistration of pilocarpine prodrug in viscous SBE7-beta-CyD solution de creases substantially eye irritation while ocular absorption is not af fected.