Molecular Recognition and Solubility of Mefenamic Acid in Water

S.K. Abdul Mudalip1, M.R. Abu Bakar2, P. Jamal3, F. Adam1,* and Z.M. Alam3

1Faculty of Chemical & Natural Resources Engineering, University Malaysia Pahang, Gambang, 26300 Kuantan, Pahang, Malaysia

2Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University Malaysia, Bandar Indera Mahkota, 25200 Kuantan, Pahang, Malaysia

3Department of Biotechnology Engineering, Kulliyyah of Engineering, International Islamic University Malaysia, 50728 Kuala Lumpur, Malaysia

*Corresponding author: Fax: +60 9 5492889; Tel: +60 9 5492824; E-mail:


Molecular dynamics simulations were performed using COMPASS force field and Ewald summation method that are available in the Material Studio simulation package. The aim of this work is to investigate the solubility and intermolecular interactions (i.e., hydrogen bonding) of water with mefenamic acid. The solubility of mefenamic acid in water is lower than the ideal solubility. The results of the simulation show that the density, diffusion coefficient and radial distribution functions calculated for water are comparable with the literature. Analysis of radial distribution functions in the binary system of mefenamic acid/water shows low hydrogen bond formation between mefenamic acid and water molecules as well as diffusivity. In addition, the strength of the interaction is much lower than that of hydrogen bonds formed between molecules of water. These findings suggest low diffusivity and poor solubility characteristic of mefenamic acid in water.


Solubility, Molecular dynamics simulation, Hydrogen bonding, Diffusivity.

Reference (32)

1.      S. Güngör, A. Yildiz, Y. Özsoy, E. Cevher and A. Araman, IL Farmaco, 58, 397 (2003); doi:10.1016/S0014-827X(03)00040-5.

2.      D.N. Bateman, Medicine, 40, 140 (2012); doi:10.1016/j.mpmed.2011.12.027.

3.      L. Fábián, N. Hamill, K.S. Eccles, H.A. Moynihan, A.R. Maguire, L. McCausland and S.E. Lawrence, Cryst. Growth Des., 11, 3522 (2011); doi:10.1021/cg200429j.

4.      S. Cesur and S. Gokbel, Cryst. Res. Technol., 43, 720 (2008); doi:10.1002/crat.200711119.

5.      R. Panchagnula, R. Sundaramurthy, O. Pillai, S. Agrawal and Y.A. Raj, J. Pharm. Sci., 93, 1019 (2004); doi:10.1002/jps.20008.

6.      S.B. Pedersen, Pharmacol. Toxicol., 75, 22 (1994); doi:10.1111/j.1600-0773.1994.tb01992.x.

7.      J.W. Mullin, Crystallization, Butterworth-Heinemann, Oxford, edn 4, (2001).

8.      S.K. Abdul Mudalip, M.R. Abu Bakar, P. Jamal and F. Adam, J. Chem. Eng. Data, 58, 3447 (2013); doi:10.1021/je400714f.

9.      J. Wang and D.R. Flanagan, Fundamentals of Dissolution, Elsevier, Burlington, MA (2009).

10.  D.C. Sperry, S.J. Thomas and E. Lobo, Mol. Pharm., 7, 1450 (2010); doi:10.1021/mp100118t.

11.  Y. Gao and K.W. Olsen, Mol. Pharm., 10, 905 (2013); doi:10.1021/mp4000212.

12.  D. Toroz, R. Hammond, K. Roberts, S. Harris and T. Ridley, J. Cryst. Growth, 401, 38 (2014); doi:10.1016/j.jcrysgro.2014.01.064.

13.  P.R. Burkholder, G.H. Purser and R.S. Cole, J. Chem. Educ., 85, 1071 (2008); doi:10.1021/ed085p1071.

14.  S.K.A. Mudalip, M.R.A. Bakar, F. Adam and P. Jamal, Int. J. Chem. Eng. Appl., 4, 124 (2013); doi:10.7763/IJCEA.2013.V4.277.

15.  Q. Yi, J. Chen, Y. Le, J. Wang, C. Xue and H. Zhao, J. Cryst. Growth, 372, 193 (2013); doi:10.1016/j.jcrysgro.2013.03.030.

16.  J. Gupta, C. Nunes, S. Vyas and S. Jonnalagadda, J. Phys. Chem. B, 115, 2014 (2011); doi:10.1021/jp108540n.

17.  H. Abdel-Halim, D. Traini, D. Hibbs, S. Gaisford and P. Young, Eur. J. Pharm. Biopharm., 78, 83 (2011); doi:10.1016/j.ejpb.2010.12.019.

18.  H. Sun, J. Phys. Chem. B, 102, 7338 (1998); doi:10.1021/jp980939v.

19.  N. Calvar, E. Gómez, B. González and Á. Domínguez, J. Chem. Thermodyn., 41, 939 (2009); doi:10.1016/j.jct.2009.03.009.

20.  A.O. Surov, I.V. Terekhova, A. Bauer-Brandl and G.L. Perlovich, Cryst. Growth Des., 9, 3265 (2009); doi:10.1021/cg900002q.

21.  M.P. Allen and D.J. Tildesey, Computer Simulation of Liquids, Oxford University Press, New York (1991).

22.  A.S. Nose, J. Chem. Phys., 81, 511 (1984); doi:10.1063/1.447334.

23.  H.J.C. Berendsen, J.P.M. Postma, W.F. van Gunsteren, A. Di Nola and J.R. Haak, J. Chem. Phys., 81, 3684 (1984); doi:10.1063/1.448118.

24.  S. Hamad, C. Moon, C.R.A. Catlow, A.T. Hulme and S.L. Price, J. Phys. Chem. B, 110, 3323 (2006); doi:10.1021/jp055982e.

25.  F. Adam, Ph.D. Thesis, Institute of Particle Technology, University of Leeds, Leeds (2012).

26.  P. Mark and L. Nilsson, J. Phys. Chem. A, 105, 9954 (2001); doi:10.1021/jp003020w.

27.  C. Chen, W.Z. Li, Y.C. Song, L.D. Weng and N. Zhang, Mol. Phys., 110, 283 (2012); doi:10.1080/00268976.2011.641602.

28.  C. Dimitroulis, E. Kainourgiakis, V. Raptis and J. Samios, J. Mol. Liq., 205, 46 (2015); doi:10.1016/j.molliq.2014.09.045.

29.  B. Lindman, G. Karlström and L. Stigsson, J. Mol. Liq., 156, 76 (2010); doi:10.1016/j.molliq.2010.04.016.

30.  S. Romero, B. Escalera and P. Bustamante, Int. J. Pharm., 178, 193 (1999); doi:10.1016/S0378-5173(98)00375-5.

31.  A.R. Leach, Molecular Modelling: Principles and Applications, Prentice Hall, England (2001).

32.  T.S. Ingebrigtsen, T.B. Schroder and J.C. Dyre, Phys. Rev. X, 2, 011011 (2012); doi:10.1103/PhysRevX.2.011011.

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