Prediction of dissolution behaviour of fumaric acid (Form B) using molecular modelling

Fumaric acid is one of stable co-former used in active pharmaceutical ingredient (APIs) drug in pharmaceutical industries. As APIs drug is known for having limited dissolution bioavailability and low solubility in water, so, one method is approach which is pharmaceutical co-crystal. Pharmaceutical co-crystal is defined as a crystalline material which consists of an API and one co-former. Basically, the aim of this research is to assess the effect of number of molecules of solvent to the dissolution of Fumaric Acid (Form B) crystal by using molecular modelling. Molecular dynamic simulation is used since the visual on how the diffusion of FUM-B into ethanol solvent can be seen. The dissolution behavior of FUM-B into ethanol solvent is determined by using mean square displacement (MSD) and diffusion coefficient (D) calculations. The results shows that the dissolution of crystal first occur at facet (0 0 1) and last dissolution occur at facet (1 -3 1) with D value of 3.866x10-9 and 2.1x10-11 respectively. The higher the value of D indicates that the faster crystal can diffuse into solvent. Facet (1 -3 1) has slow dissolution behavior because it has strong hydrogen bond interaction between crystal molecules compared to other facet. The data from simulation also analyzed by using radial distribution (RDF), the result shows as same as MSD result.