Prediction of dissolution of carbamazepine- fumaric acid co- crystal form b polymorph in ethanolic solution through molecular modelling approach

The main objectives of this study are to predict the dissolution of carbamazepine- fumaric acid (CBZ- FUM) Form B polymorph in ethanolic solution by using molecular modelling approach and to establish the interaction of ethanol molecule with co- crystal carbamazepine- fumaric acid (CBZ- FUM). In order to achieve the objectives of the research, the simulation was carried out by using Material Studio (MS) 4.4 software. The dissolution behavior of CBZ- FUM in ethanol solvent was simulated by molecular dynamic (MD) simulation. MD simulations were carried out at 571 oC and 788 oC in the NVT ensemble with simulation time of 5 ps and time step 0.1 fs, using the Berendsen thermostat. The predicted morphology has a good agreement to the experimental morphology of CBZ- FUM with 0.0020% deviation of lattice energy value between the predicted and the experimental lattice energy. For this work, the results show that the dissolution favours to occur first at the corners and edges of the crystal morphology followed by the flat surfaces of the crystal. Facet (1 1 -2) molecules located at the corner edges leave the crystal surface first into ethanol solvent phase followed by facet (1 0 -2) and lastly facet (0 1 2), and this result signifies the favourable interactions between the morphology of the crystal and the solvent is the major contributor to the dissolution process. The dissolution result also supported by coefficient diffusion and surface energy result calculated.