Design of a new multiple-unit controlled-release formulation of metoprolol ? Metoprolol CR

Abstract

A new controlled-release (CR) formulation of the beta 1-selective adrenoceptor antagonist metoprolol has been developed, aiming at an even 24-h pharmacological effect. In order to achieve this, using a once-daily dose, factors such as absorption characteristics, physicochemical properties, and technological aspects had to be considered. The new formulation, called metoprolol CR, is a disintegrating tablet consisting of several hundred coated pellets of metoprolol succinate, each pellet being its own CR delivery unit. In vitro testing and in vivo studies in healthy volunteers show that the new CR formulation gives continuous delivery of metoprolol throughout the day, resulting in smooth plasma concentration profiles, without peaks and troughs. The release of the drug is independent of pH and other physiological variables, such as food intake, which do not seem to alter the biopharmaceutical properties of the formulation.

Effects of Metoprolol CR in Patients With Ischemic and Dilated Cardiomyopathy

“…The CR formulation of metoprolol 16 was used in patients with CHF of mixed causes. Compared with the conventional metoprolol tablet, the CR formulation has Ϸ30% less bioavailability 17 ; however, a dose of 200 mg of the CR formulation caused more pronounced ␤-blockade than 150 mg of the immediate-release formulation in patients with heart failure.…”

Are All ß Blockers the Same for Heart Failure?

“…Patients were randomized to receive either placebo or metoprolol succinate controlled release/extended release (CR/XL), in addition to background therapy. This preparation of metoprolol provides more pronounced steady‐state ß blockade over the course of 24 hours 5 than the twice daily metoprolol tartrate, which may be important in protecting the heart from surges of sympathetic activity that may trigger lethal arrhythmias 6 . Showing a nearly identical result as in the CIBIS‐II, there was a 34% reduction in mortality ( p =0.00009) with metoprolol succinate.…”

Combination of Pectin and Eudargit RS and Eudragit RL in the Matrix of Pellets Prepared by Extrusion-Spheronization for Possible Colonic Delivery of 5-Amino Salicylic Acid

“…Pellets that produce by this method have benefits like narrow range of particle size, regular shape (1), maximizing drug absorption, and reducing risk of dose dumping (2). There are some variables in this technique like mixing method and time, type and amount of granulation liquid, type of extruder and spheronizer, time of spheronization, etc.…”