Dissolution Prediction of Fumaric Acid Crystal (Form A) in Ethanol using Molecular Dynamic Simulation

  • Authors

    • Siti Nurul’ain Yusop
    • Wirani Anak Nili
    • Nornizar Anuar
    • Nik Salwani Md Azmi
    • Muhammad Fitri Othman
    • Syarifah Abd Rahim
    2018-11-27
    https://doi.org/10.14419/ijet.v7i4.18.25262
  • Dissolution, fumaric acid, mean square displacement, morphology, radial distribution function.

  • Abstract

    Molecular dynamic simulation allows a better understanding on the dissolution behaviour of crystal in solvent. In this study, a dicarboxylic acid, fumaric acid crystal (Form A) is studied in ethanol which act as solvent. The morphology of fumaric acid (Form A) was successfully predicted, and the simulated lattice energy was compared with the experimental data and microphotograph of fumaric acid.  The morphology was predicted using the CVFF forcefield and the lattice energy simulated was -32.8 kcal/mol, and 4.1% deviated from the experimental lattice energy. The elongated prismatic-like shape predicted morphology was in a good agreement with the microphotograph experimental fumaric acid. Ten morphological important facets were produced; (011), (020), (100), (110), (11-1) and their multiplicity. The mean square displacement (MSD) analysis through the diffusion coefficient showed that the diffusion of molecules from the crystal facets were from the following order: (11-1) > (100) > (110) > (011) > (020), which suggested the order of detachment of molecules from the respective facets. These findings were in agreement with the detachment observations carried out at 20ps of simulation, and also with the results of attachment energies, which corresponded to the growth rate of the facets and the molecular arrangement on the facets. Meanwhile, the radial distribution function on four facets showed that the molecular interactions due to van der Waals and Coulombic charges were detected in the following order: (11-1) > (110) > (011) and (100).  

     

     

  • References

    1. [1] Aakeroy, C. B., Desper, J., Helfrich, B. A., “Heteromeric intermolecular interactions as synthetic tools for the formation of binary co-crystals,†Cryst. Eng. Comm., vol. 6, no. 5, pp. 19-24, 2004.

      [2] Adalder, T. K., Sankolli, R., Dastidar, P., “Homo-or heterosynthon? A crystallographic study on a series of new cocrystals derived from pyrazinecarboxamide and various carboxylic acids equipped with additional hydrogen bonding sites. Crystal Growth & Design, vol. 12, no. 5, pp. 2533-2542, 2012.

      [3] Martin, F. A., Pop, M. M., Borodi, G., Filip, X., Kacso, I., “Ketoconazole salt and co-crystals with enhanced aqueous solubility,†Cryst. Growth Des., vol. 13, no. 10, pp. 4295-4304, 2013.

      [4] Sarkar, A., Rohani, S., “Cocrystal of Acyclovir with promising physicochemical properties,†J. Pharm. Sci.,†vol. 104, pp. 98–105, 2015.

      [5] Rahim, S.A, Rahman, F.A, Nasir, E.N.E.M, Ramle N.A, “Carbamazepine co-crystal screening with dicarboxylic acids co-crystal formers,†Int. J. Chem. Mol. Eng., vol. 9, no.5, pp. 442-445, 2015.

      [6] Rahman, F.A., Rahim, S.A., Tan, C.C., Low, S.H., Ramle, N.A., “Carbamazepine-Fumaric Acid and Carbamazepine-Succinic Acid Co-crystal Screening Using Solution Based Method,†Int. J. Chem. Eng. Appl., vol. 8, no. 2, pp. 136-140, 2017.

      [7] Toroz, D., Hammond, R. B., Roberts, K. J., Harris, S., Ridley, T., “Molecular dynamics simulations of organic crystal dissolution: The lifetime and stability of the polymorphic forms of para-amino benzoic acid in aqueous environment.†J. Cryst. Growth, vol. 401, pp. 38-43, 2014.

      [8] Yani, Y., Chow, P. S., Tan, R. B., “Pore size effect on the stabilization of amorphous drug in a mesoporous material: Insights from molecular simulation,†Microporous Mesoporous Mater, vol. 221, pp. 117-12, 2016.

      [9] Zhang, Y., “Prediction and Theoretical Investigation of the Morphology of Erythromycin Dihydrate Crystals,†Trop. J. Pharm. Res., vol. 13, no. 6, pp. 829-834, 2014.

      [10] Rosbottom, I., Roberts, K.J., Docherty, R., “The solid state, surface and morphological properties of p-aminobenzoic acid in terms of the strength and directionality of its intermolecular synthons,†Cryst. Eng. Comm., vol. 17, pp. 5768-5788, 2015.

      [11] Hammond, R.B., Ramachandran, V., Roberts, K.J., “Molecular modelling of the incorporation of habit modifying additives: α-glycine in the presence of L-alanine,†Cryst. Eng. Comm., vol. 13, pp. 4935-4944, 2011.

      [12] Concu, R., Natalia, M., Cordeiro, D.S., “Molecular Dynamics Simulation Study of the Selectivity of a Silica Polymer for Ibuprofen,†Int. J. Mol. Sci., vol. 1083, pp. 1-11, 2016.

      [13] Shi, W., Xia, M., Lei, W., Wang, F., “Solvent effect on the crystal morphology of 2, 6-diamino-3, 5-dinitropyridine-1-oxide: A molecular dynamics simulation study,†J. Mol. Graphics Modell., vol. 50, pp. 71-77, 2014.

      [14] Berkovitch-Yellin, Z., “Toward an ab initio derivation of crystal morphology,†J. Am. Chem. Soc., vol. 107, no. 26, pp. 8239-8253, 1985.

      [15] Rao, Z., Zheng, C., Gen, F., “Proton conduction of fuel cell polymer membranes: Molecular dynamics simulation,†Comput. Mater. Sci., vol. 142, pp. 122 – 128, 2018.

      [16] Bruni, G., Maietta, M., Maggi, L., Bini, M., Capsoni, D., Ferrari, S., Marini, A., “Perphenazine–fumaric acid salts with improved solubility: preparation, physico-chemical characterization and in vitro dissolution,†Cryst. Eng. Comm., vol. 14, no. 18, 6035-6044, 2012.

      [17] Derissen, J. L., Smit, P. H., “Intermolecular interactions in crystals of carboxylic acids. IV. Empirical interatomic potential functions,†Acta Crystallogr., Sect. A: Cryst. Phys., Diffr., Theor. Gen. Crystallogr., vol. 34, no. 6, pp. 842-853, 1978.

      [18] Clydesdale, G., Roberts, K.J., Telfer, G.B., Grant, D.J.W., “Modelling the Crystal Morphology of α-Lactose Monohydrate,†J. Pharm. Sci., vol. 86, pp. 135-141, 1997.

      [19] Schmidt, C., Yϋrϋdϋ, C., Wachsmuth, A., Ulrich, J., “Modeling the Morphology of Benzoic Acid Crystals Grown from Aqueous Solution,†Cryst. Eng. Comm., 13, 1159-1169, 2011.

      [20] Anuar, N., Wan Daud, W. R., Roberts, K. J., Kamarudin, S. K., Tasirin, S. M., “Morphology and associated surface chemistry of L-isoleucine crystals modeled under the influence of L-leucine additive molecules. Cryst. Growth Des., vol. 12 no. 5, pp. 2195-2203, 2012.

      [21] Ghiolizadeh, R., Wang, Y., Yu, Y.X., “Molecular dynamic simulations of stability at the early stages.†J. Mol. Struct., vol. 1138, pp. 198-200, 2017.

  • Downloads

  • How to Cite

    Nurul’ain Yusop, S., Anak Nili, W., Anuar, N., Salwani Md Azmi, N., Fitri Othman, M., & Abd Rahim, S. (2018). Dissolution Prediction of Fumaric Acid Crystal (Form A) in Ethanol using Molecular Dynamic Simulation. International Journal of Engineering & Technology, 7(4.18), 483-487. https://doi.org/10.14419/ijet.v7i4.18.25262

    Received date: 2019-01-02

    Accepted date: 2019-01-02

    Published date: 2018-11-27