Synthesis and Physicochemical Characterization of Metoprolol Prodrugs

Author(s)

Patel, S., Mandowara, V., Gupta, D., Parejiya, P., Mehta, D., Patel, H., Shelat, P.

Author's Affiliation

Abstract

Metoprolol is widely used in the treatment of angina and hypertension. It shows great potential to treat sympathetic nervous system disorders. The success of metoprolol is limited due to its high first pass metabolism. Prodrug is one of the strategies to reduce the required dose of the drugs in order to achieve the desired bioavailability with reduced first pass metabolism. In the present study, three different prodrugs of metoprolol (metoprolol acetyl ester (MA-1), metoprolol acetamide (MA-2) and metoprolol benzamide (MA-3)) were synthesized. Further they were evaluated for physicochemical properties including solubility and partition coefficient. Ester prodrugs were found to be more soluble at pH 1.2 whereas amide prodrugs at pH 7.4 respectively showing the difference in solubility pattern. Both drug as well as prodrugs was found to be stable at pH 1.2 as compared to pH 7.4. Additionally introduction of ester and amide group in metoprolol increased the lipophillicity as observed in partition coefficient study. Prodrugs were found to be more lipophillic than metoprolol succinate. Both ester as well as amide prodrugs were found to be interesting for further in-vivo animal study.

Keywords

Prodrug, Metoprolol acetamide, Metoprolol benzamide, Physicochemical parameters, Structure elucidation

Cite This Article

Patel, S., Mandowara, V., Gupta, D., Parejiya, P., Mehta, D., Patel, H., & Shelat, P. (2016). Synthesis and Physicochemical Characterization of Metoprolol Prodrugs, International Journal for Pharmaceutical Research Scholars (IJPRS), 5(3), 12-20.