Date Published: February 01, 2019
Publisher: International Union of Crystallography
Author(s): Patrizia Rossi, Paola Paoli, Laura Chelazzi, Luca Conti, Andrea Bencini.
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.
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.