Molecular Dynamic Investigation on the Dissolution Behaviour of Carbamazepine Form III in Ethanol Solution

Abstract:

Carbamazepine (CBZ) is well known to have low solubility, hence an understanding of crystal behaviour is vital to improve the solubility of the drugs, hence for the oral bioavailability. The objectives of this work are to assess the morphology prediction of the most stable form of CBZ, which form (III) and to access the dissolution behaviour of the crystal. Material Studio 4.0 was used to predict the morphology of CBZ form (III) based on attachment energy calculations in vacuum condition by using the combination of MNDO charges from MOPAC with PCFF potential function. Later, predicted morphology was used for dissolution prediction in ethanol solvent using dynamic simulation with CVFF potential function. From the result, the morphology prediction of CBZ form (III) produced hexagonal – like shape with seven dominated facets; (011), (11-1), (100), (10-2), (020), (110) and (11-2) with the most morphological important is (011) face with 45.23% area while the fastest growing facet is (11-2) which only 0.91% area contributed to the whole crystal. The lattice energy calculated was -21.62 kcal/mol with only 1.36% error compared to the experimental value; -21.33 kcal/mol. The dissolution prediction result shows that small facet area with the amine and carbonyl groups exposed at the surface will dissolve readily than the other facets. This result explains that the small facet area with protruding functional groups that can form the hydrogen bond to ethanol molecules will be the most favourable facet to dissolve.

• Periodical: Key Engineering Materials (Volume 797)
• Pages: 149-157
• DOI: https://doi.org/10.4028/www.scientific.net/KEM.797.149
• Online since: March 2019
• Authors: Siti Nurul'ain Yusop*, Nornizar Anuar, Md Azmi Nik Salwani, Nurul Hidayah Abu Bakar
• Keywords: Carbamazepine, Mean Square Displacement, Molecular Dynamic Simulation, Morphology

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