IBUPROFEN: FROM MOLECULAR MODELING TO NANOTECHNOLOGY
Keywords:
Ibuprofen, nanoemulsion, crystallography, anti-inflammatory activity.Abstract
Ibuprofen (IBU) is a widely used nonsteroidal anti-inflammatory drug, but it has significant pharmacokinetic limitations, such as low aqueous solubility, moderate lipophilicity, and polymorphic instability, which compromise its bioavailability and clinical efficacy. This work proposes a multidisciplinary analysis of IBU, ranging from structural characterization by crystallography and molecular modeling to the development and evaluation of nanoemulsified (IBN) and emulsified (IBE) formulations. The crystal structure was investigated by X-ray diffraction, identifying polymorphic form I (space group P2₁/c), considered more thermodynamically stable (Dudognon et al., 2008). Hirshfeld surface and molecular fingerprints revealed significant intermolecular interactions, contributing to the understanding of the molecule's stability. In vivo assays were performed to compare the antinociceptive and anti-inflammatory properties of the formulations. IBN exhibited smaller particle size, reduced polydispersity index, and greater colloidal stability, resulting in superior therapeutic efficacy and reduced potential toxicity. Computational analysis indicated that the electronic structure of IBU favors its formulation in nanometric systems, due to its low polarity and moderate lipophilicity. The results demonstrate that nanoemulsion constitutes an effective strategy for overcoming the limitations of conventional formulations, increasing drug solubility, bioavailability, and stability. This study reinforces the importance of integrating structural approaches and nanotechnology in the rational development of advanced drug delivery systems.
References
ALONSO, T. R. et al. A multivariate investigation into the relationship between pharmaceutical characteristics and patient preferences of bioequivalent ibuprofen tablets. Patient Preference and Adherence, v. 12, p. 1927–1935, 2018.
CCDC - Cambridge Crystallographic Data Centre. [S.l.], 2025.
CHIENG, N.; RADES, T.; AALTONEN, J. An overview of recent studies on the analysis of pharmaceutical polymorphs. Journal of Pharmaceutical and Biomedical Analysis, v. 55, p. 618–644, 2010.
DUDOGNON, E. et al. Evidence for a new crystalline phase of racemic ibuprofen. Pharmaceutical Research, v. 25, p. 2853–2858, 2008.
GARCÍA-CELMA, M. J. et al. Improving drug delivery with nanoemulsions. Nanomedicine, v. 14, n. 3, p. 245–260, 2019.
GHOSH, I. et al. Polymorphism and poor solubility: problem and solution. PharmaSciTech, v. 1, n. 2, p. 56–63, 2011.
GUTIÉRREZ, J. M. et al. Nano-emulsions: new developments for the formulation of pharmaceuticals and cosmetics. International Journal of Pharmaceutics, v. 364, n. 2, p. 206–215, 2008.
HARTLIEB, K. J. et al. Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies. Molecular Pharmaceutics, v. 14, n. 6, p. 1831–1839, 2017.
MARTÍN, Á. et al. Production of polymorphs of ibuprofen sodium by supercritical antisolvent (SAS) precipitation. Crystal Growth & Design, v. 9, p. 2504–2511, 2009.
RAINSFORD, K. D. Ibuprofen: pharmacology, efficacy and safety. Inflammopharmacology, 2015.
ROMERO, A. L. et al. Resolução do ibuprofeno: um projeto para disciplina de química orgânica experimental. Química Nova, v. 35, n. 5, p. 1036–1040, 2012.
SANTOS, J. R. et al. Molecular modeling and solubility of olopatadine hydrochloride polymorphs. Computational and Theoretical Chemistry, v. 1224, 114110, 2023.
SHAH, P. et al. Self-emulsifying drug delivery systems (SEDDS): formulation and bioavailability considerations. Drug Development and Industrial Pharmacy, v. 36, n. 4, p. 431–441, 2010.
SOLANS, C.; SOLÉ, I. Nano-emulsions: formation by low-energy methods. Current Opinion in Colloid & Interface Science, v. 17, n. 5, p. 246–254, 2012.
VANE, J. R.; BOTTING, R. M. Mechanism of action of anti-inflammatory drugs. American Journal of Medicine, v. 104, p. 2S–8S, 1998.
