Formulation and evaluation of new long acting metoprolol tartrate ophthalmic gels

The rationale of the present work is to formulate and evaluate metoprolol tartrate (MT), which is a beta-1 selective adrenergic blocking agent in a new ocular gel delivery system; this is our way and method to increase its contact to the cornea, giving a longer time of drug contact to the eye and slow possible release from the preparation. Metoprolol tartrate is chosen as a candidate for gel formulation because although it has been available for a few years as ophthalmic solutions, it has not been marketed as an ocular gel yet. Two polymers; Carbopol 934 and Pluronic F127 (PF127) were used in two different concentrations in this study. Metoprolol tartrate was used in two concentrations, 0.5% and 1% (w/w). All formulations were exposed to visual examinations, pH measurement, in vitro release, rheological study and differential scanning calorimetry (DSC). Results showed that all formulations were clear, showed pH within the acceptable range suitable to be administered in the eye, and exhibited pseudoplastic flow behavior. DSC results concluded that, MT was compatible with different polymers used. In vitro release results showed that the release rate of metoprolol tartrate from gel preparations decreased as an inverse function of polymer concentration, and the release rate of the drug increased as the initial concentration increased. Intra-ocular pressure (IOP) measurements of rabbit's eye treated with 1% (w/w) metoprolol tartrate in gel formulations with different concentrations of the polymer were determined. Carbopol 934 gel formulations showed that this polymer extended the duration of pressure reducing effect of MT to more than 5hr when compared with Pluronic F127 gel formulations. The area above the curve (AAC), maximum response, time of maximum response (t max), and the duration of the drug action were also calculated.