In Vitro And In Vivo Evaluation Of Controlled-Release Buccoadhesive Disks Of Timolol Maleate

Abstract

The aim of the present work was to develop a buccoadhesive controlled-release dosage form of timolol maleate (TM) and to evaluate the feasibility of improving the bioavailability of TM via the buccal route. Buccoadhesive disks (BDs) of TM were prepared by the direct compression method using some selective polymers like carbopol 934(CP 934) and hydroxypropyl methylcellulose (HPMC K4M) in different amounts along with other tablet excipients. The disks were evaluated for thickness uniformity, weight variation, drug content uniformity, hardness, friability and surface pH. The buccal permeability of TM was assessed in one human subject and the drug was found to permeate through the buccal mucosa. The BDs were also evaluated for swelling index and bioadhesion time using rabbit buccal tissues. The swelling index was found to increase with an increase in HPMC and CP content in the disks and none of the disks detached from the rabbit buccal tissues until completely eroded. The in vitro drug release for 12 h in pH 6.6 phosphate buffer using a USP dissolution tester revealed that the rate of drug release was increased when the polymers were incorporated in the disks at low concentrations, but was decreased when incorporated at higher concentrations. When the release data were evaluated by a simple power equation (Mt/M = ktn); it was observed that drug release from most of the formulated BDs followed non-fickian release kinetics. A selected BD formulation was evaluated in vivo in rabbits. The selected BD gave controlled blood level profile with a 50% increase in area-under-the-curve (AUC) value in comparison to oral administration of aqueous drug solution.

Egyptian Journal of Biomedical Sciences Vol. 23 (1) 2007: pp. 196-217