Simultaneous delivery of Nifedipine and Metoprolol tartarate using sandwiched osmotic pump tablet system

Abstract

The sandwiched osmotic tablet system that could deliver Nifedipine and Metoprolol tartarate simultaneously for extended period of time was developed in order to reduce the problems associated with multidrug therapy of hypertension. This system composed of a middle push layer and attached drug layers of Nifedipine and Metoprolol. The advantage of the sandwiched osmotic tablet system over the commercialized push–pull osmotic tablet system is its simplicity of preparation, as the surface identification was avoided. Polyethylene oxide 600,000 and 8,000,000 g/mole were used as thickening agent of drug layer and the expandable hydrogel of push layer, respectively. It has been observed that amount of polyethylene oxide (PEO) and KCL of the drug and push layer had profound influence on Nifedipine and Metoprolol release. Further, the release of drugs was optimized by the size of the delivery orifice, level of plasticizer and membrane thickness. The optimal osmotic pump tablet was found to deliver both drugs at a rate of approximately zero order for up to 16 h independent of pH and agitational intensity, but dependent on the osmotic pressure of the release media. The formulations were found to be stable after 3 months of accelerated stability studies. Prediction of steady-state levels showed the plasma concentrations of Nifedipine and Metoprolol to be within the desired range. Further sandwiched system had a good sustained effect in comparison with the conventional product. Hence the prototype design of the system could be applied to other combinations of drugs used for cardiovascular diseases, diabetes, etc.