Physical Mixture Interaction of Acetaminophenol with Naringenin

Normyzatul Akmal Abd Malek(1*), Hamizah Mohd Zaki(2), Mohammad Noor Jalil(3)

(1) Atta Ur Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam, Bandar Puncak Alam, 42300, Selangor, Malaysia Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, 40000, Shah Alam, Selangor, Malaysia
(2) Atta Ur Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Puncak Alam, Bandar Puncak Alam, 42300, Selangor, Malaysia Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, 40000, Shah Alam, Selangor, Malaysia
(3) Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam, 40000, Shah Alam, Selangor, Malaysia
(*) Corresponding Author


The interaction of Active Pharmaceutical Ingredient (API) with other compounds will affect drugs stability, toxicity, modified dissolution profiles or may form a new compound with the different crystal structure. Acetaminophenol (APAP), the most common drug used widely (also known as Panadol) was mixed with Naringenin (NR) to glance for a new phase of interactions leading to new compound phase. The amide-acid supramolecular heterosynthon; N-HO interaction between acid and the respective base were observed in the APAP-NR mixture blends. The interaction was prepared by the binary interaction from neat grinding and liquid-assisted grinding techniques at a different stoichiometry of binary mixture ratio of APAP-NR which were 1:1, 1:2 and 2:1 molar ratio. The interaction was estimated using Group Contribution Method (GCM) and physicochemical properties were characterized by Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR), powder X-ray diffraction (PXRD) and Differential Scanning Calorimetry (DSC) analysis. The GCM calculation gave good interaction strength at 212.93 MPa1/2. The ATR-FTIR, DSC and PXRD results obtained revealed an interaction with new phase formed.


neat grinding; acetaminophenol; Naringenin; intermolecular interaction

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[1] Semalty, A., Semalty, M., Singh, D., and Rawat, M.S.M., 2010, Preparation and characterization of phospholipid complexes of naringenin for effective drug delivery, J. Inclusion Phenom.Macrocyclic Chem., 67 (3-4), 253–260.

[2] Almalki, A.S.A., Naglah, A.M., Refat, M.S., Hegab, M.S., Adam, A.M.A., and Al-Omar, M.A., 2017, Liquid and solid-state study of antioxidant quercetin donor and TCNE acceptor interaction: Focusing on solvent effect on the morphological properties, J. Mol. Liq., 233, 292–302.

[3] Al-Zoubi, N., Koundourellis, J.E., and Malamataris, S., 2002, FT-IR and Raman spectroscopic methods for identification and quantitation of orthorhombic and monoclinic paracetamol in powder mixes, J. Pharm. Biomed. Anal., 29 (3), 459–467.

[4] Middleton, E., 1994, “The Impact of Plant Flavonoids on Mammalian Biology: Implications for Immunity, Inflammation and Cancer” in The Flavonoids, Advances in Research since 1986, Harborne, J.B., eds., Chapman & Hall, London, U.K., 619–652.

[5] Hertog, M.G., Hollman, P.C., Katan, M.B., and Kromhout D., 1993, Intake of potentially anticarcinogenic flavonoids and their determinants in adults in the Netherlands, Nutr. Cancer, 20 (1), 21–29.

[6] Burgina, E.B., Baltakhinov, V.P., Boldyreva, E.V., and Shakhtschneider, T.P., 2004, IR spectra of paracetamol and phenancetin. 1. Theoretical and experimental studies, J. Struct. Chem., 45, 64–73.

[7] Chua, L.S., Latiff, N.A., Lee, S.Y., Lee, C.T., Sarmidi, M.R., and Aziz, R.A., 2011, Flavonoids and phenolic acids from Labisia pumila (Kacip Fatimah), Food Chem., 127 (3), 1186–1192.

[8] de Villiers, M.M., Wurster, D.E., Van der Watt, J.G., and Ketkar, A., 1998, X-Ray powder diffraction determination of the relative amount of crystalline acetaminophen in solid dispersions with polyvinylpyrrolidone, Int. J. Pharm., 163 (1-2), 219–224.

[9] Norhaiza, M., Maziah, M., and Hakiman, M., 2009, Antioxidative properties of leaf extracts of a popular Malaysian herb, Labisia pumila, J. Med. Plants Res., 3 (4), 217–223.

[10] Hancock, B.C., York, P., and Rowe, R.C., 1997, The use of solubility parameters in pharmaceutical dosage form design, Int. J. Pharm., 148 (1), 1–21.

[11] Hiendrawan, S., Veriansyah, B., Widjojokusumo, E., Soewandhi, S.N., Wikarsa, S., and Tjandrawinata, R.R., 2016, Physicochemical and mechanical properties of paracetamol cocrystal with 5-nitroisophthalic acid, Int. J. Pharm., 497 (1-2), 106–113.

[12] Kachrimanis, K., Braun, D.E., and Griesser, U.J., 2007, Quantitative analysis of paracetamol polymorphs in powder mixtures by FT-Raman spectroscopy and PLS regression, J. Pharm. Biomed. Anal., 43 (2), 407–412.

[13] Mohd Zaki, H., 2011, Spectroscopy Surface Analysis of Paracetamol and Paracetamol and Excipient Systems, Thesis, University of Manchester.

[14] Wegiel, L.A., Mauer, L.J., Edgar, K.J., and Taylor, L.S., 2013, Crystallization of amorphous solid dispersions of resveratrol during preparation and storage—Impact of different polymers, J. Pharm. Sci., 102 (1), 171–184.

[15] Wen, J., Liu, B., Yuan, E., Ma, Y., and Zhu, Y., 2010, Preparation and physicochemical properties of the complex of naringenin with hydroxypropyl-β-cyclodextrin, Molecules, 15 (6), 4401–4407.

[16] Felgines, C., Texier, O., Morand, C., Manach, C., Scalbert, A., Régerat, F., and Rémésy, C., 2000, Bioavailability of the flavanone naringenin and its glycosides in rats, Am. J. Physiol. Gastrointest. Liver Physiol., 279 (6), G1148–G1154.

[17] Kaialy, W., Larhrib, H., Chikwanha, B., Shojaee, S., and Nokhodchi, A., 2014, An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression, Int. J. Pharm., 464 (1-2), 53–64.

[18] Pathak, C.D., Savjani, K.T., Gajjar, A.K., and Savjani, J.K., 2013, Cocrystal formation of paracetamol with indomethacin and mefenamic acid: An efficient approach to enhance solubility, Int. J. Pharm. Pharm. Sci., 5 (4), 414–419.

[19] Xu, X.R., Yu, H.T., Hang, L., Shao, Y., Ding, S.H., and Yang, X.W., 2014, Preparation of naringenin/β-cyclodextrin complex and its more potent alleviative effect on choroidal neovascularization in rats, BioMed Res. Int., 2014, 623509.

[20] Pralhad, T., and Rajendrakumar, K., 2004, Study of freeze-dried quercetin–cyclodextrin binary systems by DSC, FT-IR, X-ray diffraction and SEM analysis, J. Pharm. Biomed. Anal., 34 (2), 333–339.


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