Development of A New Controlled Release Metoprolol Product

Abstract

A new controlled-release preparation intended for once-daily dosage has been developed for the β-selective adrenoreceptor antagonist metoprolol. The scope of this presentation is to discuss biopharmaceutical and technical considerations in the development of the product. Metoprolol is well absorbed from the entire gastro-intestinal tract. In-vitro/in-vivo correlation studies showed that a pH-independent and constant (zero-order) release during about 20 hours was suitable for the final preparation. A “multiple-unit” tablet consisting of several hundred coated metoprolol pellets was developed. Desired release properties were obtained by choosing a suitable salt (succinate), preparing compact pellets without soluble additives and coating the pellets with a pH-independent polymeric layer. The final preparation has shown good manufacturing reproducibility and produces uniform plasma concentration-time curves in vivo.