Ocular pharmacokinetics of methazolamide ophthalmic suspension in rabbit aqueous humor

Methazolamide (MTZ) is a carbonic anhydrase inhibitor widely used in oral administration in the treatment of glaucoma.Topical formulations of MTZ ophthalmic suspension were developed to avoid the systemic side-effects.Micronized drug obtained by ball milling was suspended in the solutions of Carbopol 940 (Formulation 1) or Carbopol 974 (Formulation 2) of appropriate concentrations to develop uniform and stable MTZ ophthalmic suspension.The pharmacokinetic profiles of the ophthalmic suspensions in rabbit aqueous humor were investigated by the microdialysis technique using orally administered MTZ tablets as the control.It was shown in aqueous humor that the pharmacokinetic parameters (AUC，c_max，and t_max) of Formulation 1 (with 0.4% Carbopol 940) were estimated to be (109 838.3±28 081.26) ng ·min/mL，(1 535.60±125.75) ng/mL，and (50±8.66) min，respectively；those of Formulation 2 (with 0.45% Carbopol 974) (116 803.1±21 015.71) ng ·min/mL，(1 399.78±136.45) ng/mL，and (30±0.00) min，respectively；those of MTZ tablets (59 197.07±10 020.72) ng ·min/mL，(313.96±6.57) ng/mL，and (85±17.32) min，respectively.In addition，AUCs of Formulation 1 and Formulation 2 were 1.86 and 1.97 times higher than that of the control group，respectively (P<0.05).These results indicate that the ophthalmic suspensions increased the bioavailability of MTZ in the eye aqueous humor，which is of significance in the development of topical dosage form of MTZ.