dorzolamide and hydroxyethylcellulose

A three-dose, randomized, double-blind parallel, placebo-controlled ocular tolerancy study was undertaken in 24 healthy, normal volunteers with two formulations of 2% MK-507 (L-671 152), a novel water-soluble, topical carbonic anhydrase inhibitor. In this study MK-507 was administered to humans for the first time. Subjects received 3 sequential drops of the test drug in one randomly selected eye (at 13:00, 14:00, and 14:10 o'clock): ten received 2% MK-507 formulated with 0.5% hydroxyethylcellulose (HEC); ten, 2% MK-507 with no HEC; two, vehicle with HEC; and two, vehicle without HEC. Local tolerance of 2% MK-507 was good with predominantly mild and transient local symptoms, somewhat fewer for the formulation without HEC. Significant lowering of intraocular pressure (IOP) by up to 7 mmHg was noted when comparing IOP 4 h and 5 h after the first dose with IOP 20 h and 19 h before the first dose in the treated eyes of subjects receiving MK-507. Slightly greater activity was noted when MK-507 was formulated with HEC.

Topics: Adult; Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Cellulose; Double-Blind Method; Humans; Male; Ophthalmic Solutions; Sulfonamides; Thiophenes

Eye drops containing hydrophilic drugs are commonly used to reduce intraocular pressure (IOP) in glaucoma patients, but compliance to the treatement is commonly reduced by frequent dosing and eventual systemic side effects. Sustained-release drug delivery systems, such as ocular inserts, can reduce dosing, limit systemic exposure, reduce side effects, and, then, improve patient adherence to therapy. Here, we developed and evaluated chitosan/hydroxyethyl cellulose-based ocular inserts for sustained release of dorzolamide, a hydrophilic drug. Dorzolamide inserts (DI) were produced by solvent/casting method and characterized by various physicochemical techniques. Pharmacokinetics studies were performed using scintigraphic images and ex vivo biodistribution. The effectiveness of inserts was tested in glaucomatous rats. Characterization studies showed that the drug strongly interacted with the polymeric matrix, but in vitro results showed that DI took only 3 h to release 75% of dorzolamide entraped. However, scintigraphic images and ex vivo biodistribution studies revealed that more than 50% of

Topics: Animals; Cellulose; Chitosan; Delayed-Action Preparations; Drug Delivery Systems; Eye; Glaucoma; Intraocular Pressure; Male; Ophthalmic Solutions; Polymers; Rats; Rats, Wistar; Sulfonamides; Thiophenes; Tissue Distribution