Investigating Differences and Similarities between Betaxolol Polymorphs

Abstract

Betaxolol belongs to the class of β1-adrenergic blocking agent. Several polymorphs of racemic betaxolol have been reported in the literature, but only one of them (BE_I) had the crystal structure determined from single-crystal X-ray diffraction. Here, we present a new crystalline phase of betaxolol (BE_IV). Its solid-state structure has been obtained from single-crystal X-ray diffraction data. The molecular and crystal arrangements of betaxolol in BE_IV have been further investigated by molecular modelling, by Cambridge Structural Database (CSD) surveys and by Hirshfeld surface analysis. A comparison with the solid-state structure of BE_I have been carried out. In the two polymorphs the 2-hydroxy-3-(isopropylamino)-propoxy chain, which is common to other β-blocker drugs, adopts a different conformation. In addition, the rotational isomer found in BE_IV is different with respect to the four already observed in the solid-state structure of analogous compounds. In both the polymorphs, the most significant interaction is due to the H-bonds involving the OH group as donor and the NH as acceptor, while the interaction where OH works as acceptor (NH acts as donor) is definitely less important. The resulting H-bond patterns are however different: Alternate R2,2(10) a > a (OH donors) and R2,2(10) b > b (OH acceptors) in BE_I vs. alternate R4,4 (8) a > b > a > b (OH donors) and R2,2 (10) b > b (OH acceptor) in BE_IV.

Nonsteroidal Anti-Inflammatory Drugs–1-Phenylethylamine Diastereomeric Salts: A Systematic Solid-State Investigation

“…In the past, we have used X-ray diffraction (SCXRD, PXRD) thermoanalytical techniques (DSC, TGA, and HSM) and in-silico tools (e.g., modeling and data mining) to study the solid forms of APIs belonging to different classes (β-blockers, , NSAIDs) and in different forms (salts − and metal complexes) and to correlate their structural and physicochemical properties. , …”

“…In the past, we have used X-ray diffraction (SCXRD, PXRD) thermoanalytical techniques (DSC, TGA, and HSM) and insilico tools (e.g., modeling and data mining) to study the solid forms of APIs belonging to different classes (β-blockers, 11,12 NSAIDs) and in different forms (salts 13−15 and metal complexes) 16 and to correlate their structural and physicochemical properties. 17,18 With this in mind, and as part of our ongoing structural study of (S)-ketoprofen (S-Ket, hereafter), 19−21 its DSs with (R)-(+)-and (S)-(−)-1-phenylethylamine (α-methylbenzylamine; R-PEA and S-PEA, hereafter, Scheme 1) were prepared and investigated.…”

Rationalization of Lattice Thermal Expansion for Beta-Blocker Organic Crystals

“…showed that the metoprolol free base undergoes an anisotropic thermal expansion [8], while the polymorph I of the closely related β-blocker drug betaxolol [9] (see scheme 1) that gives rise to almost identical H-bond motifs ( (10), vide infra) [10] (see Figure 1) shows an isotropic thermal expansion. The same holds for polymorph IV of betaxolol [11], i.e., its crystal lattice isotropically expands/contracts on changing the temperature; however, in this case, the H-bond network is slightly different (alternating (10) and (8) patterns).…”

Molecular-Level Investigation of Hydrate–Anhydrous Phase Transformations of the Dapsone Structurally Related Compound 3,3′-Diaminophenyl Sulfone

“…In particular, valuable information on the molecular and crystal structures of the corresponding crystalline solids have been extracted and correlated to their properties, e.g. , isotropic vs anisotropic thermal expansion, − chiral recognition, phase stability/transformation, solvation/desolvation processes, − and polymorphic behavior. − …”