Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation

Abstract

The design of new pharmaceutical solids with improved physical and chemical properties can be reached through in-detail knowledge of the noncovalent intermolecular interactions between the molecules in the context of crystal packing. Although crystallization from solutions is well-known for obtaining new solids, the effect of some variables on crystallization is not yet thoroughly understood. Among these variables, solvents are noteworthy. In this context, the present study aimed to investigate the effect of ethanol (EtOH), acetonitrile (MeCN), and acetone (ACTN) on obtaining irbesartan (IBS) crystal forms with 2,3-dibromosuccinic acid. Crystal structures were solved by single-crystal diffraction, and the intermolecular interactions were analyzed using the Hirshfeld surfaces analysis. The characterization of physicochemical properties was carried out by powder X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), thermal analysis, and solution-state NMR techniques. Two different IBS salts were obtained, one from MeCN and ACTN (compound 1 ) and a different one from EtOH (compound 2 ). The experimental results were in agreement with the findings obtained through quantum mechanics continuum solvation models. Compound 1 crystallized as a monoclinic system P 2 1 / c , whereas compound 2 in a triclinic system P 1̅. In both structures, a net of strong hydrogen bonds is present, and their existence was confirmed by the FT-IR results. In addition, the IBS cation acts as a H-bond donor through the N1 and N6 nitrogen atoms which interact with the bromide anion and the water molecule O1W in compound 1 . Meanwhile, N1 and N6 nitrogen atoms interact with the oxygen atoms provided by two symmetry-related 2,3-dibromo succinate anions in compound 2 . Solution-state NMR data agreed with the protonation of the imidazolone ring in the crystal structure of compound 1. Both salts presented a different thermal behavior not only in melting temperature but also in thermal stability.

Novel Synthesis and Characterization of Irbesartan Derivative an Anti‐Hypertensive Active Pharmaceutical Ingredient (API)

“…We encouraged by the results of previous research on synthetic modification of Diclofenac, undertook irbesartan for the current research and it highlights the novel synthetic methodology to prepare acetyl and chloroacetyl derivatives of commercially available drug Irbesartan. [8][9][10][11][12] It is a biphenyl tetrazole and an azaspiro compound, IUPAC name is 2-butyl-3- [4.4] non-1-en-4one. [13] Non-peptide angiotensin II receptor blockers (ARBs) are a class of medication used to treat heart failure and excessive blood pressure.…”

The Same but Not the Same: The Case of (S)-Naproxen/cis-1-Amino-2-indanol Chiral Resolution via Diastereomeric Salt Formation

“…Choosing the most appropriate resolving agent can be tricky and time-consuming so that it is often widely empirical. X-ray diffraction, along with various thermoanalytical techniques and in silico approaches, serves as an essential tool for exploring the forces and interactions in crystal packing, − hence playing a crucial role in understanding the driving forces behind the formation of structurally related diastereomeric salts. − …”

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. − …”