Application of Box-Behnken Design to Optimize the Osmotic Drug Delivery System of Metoprolol Succinate and its In Vivo Evaluation in Beagle Dogs

The objective of this study was to develop osmotic pump tablets of metoprolol succinate (MS) using water-soluble pore formers in the semipermeable membrane in place of orifice drilled on the membrane thereby abolishing the shortcomings associated with laser drilling technique. The formulation was optimized for coating variables such as semipermeable membrane level (X-1) and pore former level (X-2) by response surface methodology using Box-Behnken design (BBD) employing design expert software. The developed osmotic pump tablet was found to sustain the drug release up to 20 h at zero-order rate. The pharmacokinetic study in Beagle dogs showed delayed T-max and lower C-max compared to marketed brand TOPROL XL, indicating a slow and more sustained release behavior of MS from the optimized osmotic tablets in comparison with the existing matrix-based marketed dosage form. Thus, a novel approach for the controlled release of MS from osmotic pump tablets has been successfully developed using BBD, which is valuable for the advancement of controlled drug delivery of other water-soluble drugs.