Formulation and evaluation of ophthalmic preparations of acetazolamide

The orally administered acetazolamide has a limited use in glaucoma due to the systemic side effects associated with its use. It has been reported to show little effect on the intraocular pressure(IOP) of human and rabbit eye s upon topical application, probably owing to its poor bioavailability and instability at pH > 5.0. In order to enhance the bioavailability of the dru g, contact time between the drug molecules and the ocular surface was incre ased using high viscosity, water soluble polymers (PVA, HPMC), and by incor porating acetazolamide into an in situ-forming ophthalmic drug delivery sys tem. Moreover, a penetration enhancer (EDTA) was also used in these formula tions to increase the extent of absorption of the drug. Acetazolamide at a concentration of 10% was used and the formulations (eyedrop suspensions) we re evaluated for their in vitro release pattern. The effect of these formul ations on the IOP in normotensive conscious rabbits was also investigated. These formulations were found to be therapeutically effective with a peak e ffect at 2 h. A fall in IOP of up to 46.4% was observed with repeated admin istration of one of the formulation containing PVA, EDTA and Tween 80 (MK-5 ). Results indicated that a topical effect of acetazolamide can be observed if the formulation, (a) contains a suitable polymer-to increase the reside nce time; (b) a penetration enhancer-as acetazolamide has a low permeabilit y coefficient i.e. 4.1 x 10(-6) cm/s [Duffel, M.W., Ing. I.S., Segarra, T.M ., Dixson, J.A., Barfknecht, C.F,, Schoenwald, R.D., 1986. J. Med. Chem. 29 . 1488-1494]; and (c) pH of the Formulation is maintained at the point of m aximum stability (pH less than or equal to 5.0). (C) 2000 Elsevier Science B.V. All rights reserved.