betadex and Miosis

The objective of this prospective study was to determine the effects of a single intravenous bolus of alfaxalone in 2-hydroxypropyl-β-cyclodextrin and propofol on the intraocular pressure (IOP) in sheep. Ten Ripollesa sheep with a bodyweight of 48.5 (6.8) kg (mean [sd]) were used in the study. Twenty-four hours before the experimental procedure, a complete ophthalmic examination was performed in all animals. The day of the study, intravenous alfaxalone (2 mg/kg) or propofol (6 mg/kg) was randomly administered in a cross-over design, with a washout period of two weeks. Measurements of IOP, globe position and pupil size were obtained at basal time, before induction (time 0) and at two, five, 10, 15, 20, 30, 45, 60, 90 and 120 minutes after drug administration. Occasional side effects and time to standing were also noted. Intravenous administration of alfaxalone and propofol in sheep resulted in no alteration of IOP. Nevertheless, a decrease in the pupil size was observed in both groups. This present study shows that alfaxalone and propofol, administrated as a single intravenous bolus, are good options for maintaining IOP during anaesthesia in sheep, although marked miosis was observed after administration.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Anesthetics, Intravenous; Animals; beta-Cyclodextrins; Cross-Over Studies; Infusions, Intravenous; Intraocular Pressure; Miosis; Pregnanediones; Propofol; Prospective Studies; Pupil; Sheep; Time Factors

The complexation of pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpate, with various beta-cyclodextrin (beta-CyD) derivatives was studied by the phase solubility method. The effects of coadministered sulphobutyl ether beta-CyD (SBE7-beta-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 beta-CyD (SBE4-beta-CyD and SBE7-beta-CyD), and 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. Ocular absorption of the prodrug was improved by increasing the viscosity of prodrug/SBE7-beta-CyD solution with PVA without inducing any eye irritation. Eye irritation due to viscous prodrug/SBE7-beta-CyD solutions was comparable with isotonic NaCl solution. We conclude that administration of pilocarpine prodrug in viscous SBE7-beta-CyD solution decreases substantially eye irritation while ocular absorption is not affected.

Topics: Animals; beta-Cyclodextrins; Cyclodextrins; Drug Tolerance; Eye; Miosis; Pharmaceutical Vehicles; Pilocarpine; Prodrugs; Rabbits

The influence of buffer, viscosity and cyclodextrin on the ocular absorption and irritation of a pilocarpine prodrug, O,O'-dipropionyl-(1,4-xylylene) bispilocarpic acid diester, was studied in albino rabbits. The prodrug solutions, equivalent to 0.5% pilocarpine, were prepared in 0, 10, 20, 50, or 75 mM citrate buffer at pH 5.0. Viscosity of the solutions (20, 50 or 115 cP) was modified with hydroxypropyl methylcellulose. 2-hydroxypropyl-beta-cyclodextrin (HPCD) was included at concentrations 5, 10 and 15% (w/v). The formulations were compared to a commercial pilocarpine eyedrop (1.7%). Ocular irritation was graded in a double-masked experiment and miosis was used as a bioassay for pilocarpine delivery to the iris. The prodrug showed decreased peak and prolonged duration of miosis compared to pilocarpine, but it caused ocular irritation. Increasing buffer strength decreased and elevated viscosity intensified the miotic response and irritation by the pilocarpine prodrug. HPCD decreased both the ocular delivery of pilocarpine and the irritation by the prodrug, but the net effect was positive. Thus, administering 1.0% of pilocarpine as a prodrug with 15% (w/v) HPCD, the irritation was at the same level with the commercial pilocarpine eyedrop, but the ocular delivery was substantially improved. In conclusion, the ocular delivery of the pilocarpine prodrug may be enhanced in relation to its local irritation by properly combining buffer, viscosity and HPCD.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Absorption; Animals; beta-Cyclodextrins; Biological Availability; Buffers; Cyclodextrins; Eye; Female; Irritants; Male; Miosis; Ophthalmic Solutions; Pilocarpine; Prodrugs; Rabbits