Solubility enhancement and structural insights into pipemidic acid via salt formation with benzoic acid

Shwetha Jayapura Chandrashekar; Rajalakshmanan Eswaramoorthy; Kamalakaran Anand Solomon

doi:10.5155/eurjchem.16.2.104-116.2631

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Published: Jun 30, 2025

DOI: https://doi.org/10.5155/eurjchem.16.2.104-116.2631

Keywords:

Solubility, Benzoic acid, Pipimedic acid, Dissolution rate, Hirshfeld surface analysis, Single-crystal X-ray diffraction

Section

Research Article

Issue

Vol. 16 No. 2 (2025): June 2025

Dates

Received 2025-01-06
Accepted 2025-04-23
Published 2025-06-30

Shwetha Jayapura Chandrashekar

Department of Physical and Chemical Science, Sri Sathya Sai University for Human Excellence, Navanihal, Kalaburagi, 585313, Karnataka, India

https://orcid.org/0000-0002-3262-7583

Rajalakshmanan Eswaramoorthy

Centre of Molecular Medicine and Diagnostics, Department of Biochemistry, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, 600077, Chennai, India

https://orcid.org/0000-0002-8331-2100

Kamalakaran Anand Solomon

Department of Chemistry, School of Engineering, Dayananda Sagar University, Devarakaggalahalli, Harohalli, Kanakapura Road, Dt, Ramanagara, 562112, Karnataka, India

https://orcid.org/0000-0003-4677-2340

Abstract

Pipemidic acid (PMA) is an active pharmaceutical ingredient (API) belonging to the quinolone class of antibacterial agents, primarily used to treat urinary tract infections. This study investigated improving the dissolution properties of poorly soluble PMA by forming a 1:1 stoichiometry molecular salt (4BA) with benzoic acid (BA). Liquid-assisted grinding and slow evaporation techniques were used to prepare the solid form of the salt. The salt was then characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), and single-crystal X-ray diffraction (SC-XRD). The DSC analysis provided information on the changes in thermal behavior associated with the formation of the salt. FTIR spectroscopy helped identify the functional groups present and potential interactions between PMA and benzoic acid. SC-XRD determined the definitive three-dimensional arrangement of atoms within the salt structure, revealing a wave-like hydrogen bonding network directing a 3D layered packing of molecules. This improved packing is believed to be responsible for the improved solubility of PMA in the salt form. The Hirshfeld surface analysis, along with its associated 2D fingerprint plots, further elucidated the intermolecular interactions within the crystal lattice. This analysis showed that, in addition to the strong N-H···O and O-H···O hydrogen bonds, weaker H···H, C···H, and H···C interactions also play a significant role in stabilizing the molecular packing. Finally, cumulative drug release (CDR) showed that the formation of the molecular salt significantly improved the dissolution behavior of PMA, potentially leading to sustained drug release.

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Chandrashekar, S. J.; Eswaramoorthy, R.; Solomon, K. A. Solubility Enhancement and Structural Insights into Pipemidic Acid via Salt Formation With Benzoic Acid. Eur. J. Chem. 2025, 16, 104-116.

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