Prediction of carbamazepine-succinic acid as co-crystal dissolution in ethanolic solution using computational molecular dynamic simulation technique

Carbamazepine (CBZ) famously known to be analgesic and anticonvulsant with solubility and polymorphism problem had become a great challenge to crystal engineers since their crystal packing were unpredictable. CBZ forms supramolecular complexes with co-crystal former, succinic acid (SA) which are complementary with each other in terms of hydrogen bonding. This approach thoroughly modifies the crystal packing and affect the physical and pharmaceutical properties of CBZ. The interaction occur between carbamazepine and the succinic acid can be predicted by using a molecular dynamic simulation technique. Carbamazepine-succinic acid (CBZ-SA) co-crystal morphology that consist of seven dominant facets was cleaved to gain better insights on the interaction, which later affects the dissolution behaviour of the crystal. Hydrogen bonding is the key of interaction in the crystal engineering. Thus, accessing the interaction between one reference atom and ethanol with one unit cell of carbamazepine-succinic acid (CBZ-SA) co-crystal was the main objective. The plate-like shape morphology of CBZ-SA co-crystal consist of seven dominant facets which were (1 0 -1), (1 0 1), (1 1 0), (0 1 1), (0 1 0), (2 0 0) and (0 0 2). In order to study the stability phenomenon, two aspects were analyzed: (1) Radial distribution function (RDF), (2) Mean square displacement (MSD). Each molecules in each facets exhibit different type of interaction with the reference molecule and ethanol molecule..