Research Article: The solid-state structure of the β-blocker metoprolol: a combined experimental and in silico investigation

Date Published: February 01, 2019

Publisher: International Union of Crystallography

Author(s): Patrizia Rossi, Paola Paoli, Laura Chelazzi, Luca Conti, Andrea Bencini.

http://doi.org/10.1107/S2053229618017084

Abstract

The metoprolol free base has been characterized in the solid state by X-ray diffaction (both single-crystal and variable-temperature powder diffraction) and differential scanning calorimetry. These studies are supplemented by mol­ecular modelling and Hirshfeld surface analysis. Structural relationships with the strictly related betaxolol are discussed.

Partial Text

Metoprolol, or (RS)-1-iso­propyl­amino-3-[4-(2-meth­oxy­eth­yl)phen­oxy]propan-2-ol (see a in Scheme 1), is a cardioselective β1-adrenergic blocking agent that has numerous medical applications, such as the treatment of acute myocardial infarction, heart failure, angina pectoris and hypertension (Benfield et al., 1986 ▸; Brogden et al., 1977 ▸). The drug is usually manufactured as a racemic mixture, notwithstanding the fact that the β1-blocking activity resides in the S enatiomer (Dasbiswas et al., 2008 ▸). In addition, given its quite low melting point (323 K) (Ionescu et al., 2006 ▸), metoprolol is always marketed in salt-based formulations (i.e. tartrate, succinate and fumarate) that differ in the drug-release mechanism (Wikstrand et al., 2003 ▸). According to the Biopharmaceutics Classification Scheme, metoprolol belongs to the class I substances (Amidon et al., 1995 ▸), meaning that it has both high aqueous solubility and intestinal permeability, which makes this API (active pharmaceutical ingredient) suitable for Extended Release (ER) formulations.

Metoprolol tartrate and betaxolol hydro­chloride were purchased from Sigma–Aldrich (product codes M5391-10G and B5683-50MG, respectively) and used without further purification.

 

Source:

http://doi.org/10.1107/S2053229618017084

 

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