IMPACT OF SOLVENT FUNCTIONAL GROUPS ON INTERMOLECULAR INTERACTIONS AT CRYSTAL GROWTH SURFACES OF FORM II PARACETAMOL
DOI:
https://doi.org/10.11113/jurnalteknologi.v88.23734Keywords:
Form II paracetamol, crystallisation, functional group, intermolecular interactions, morphologyAbstract
Crystals grown in specific solvents can be designed with desired shapes by understanding interactions between solvent functional groups and crystal surfaces. This is crucial for the successful design and operation of crystallisation processes, preventing issues with undesired products that can lead to manufacturing challenges like difficulty in filtration, granulation, and tabletting. This study investigated the influence of solvent functional groups on the crystal morphology of Form II paracetamol using molecular modelling techniques. The interaction energies between the solvent molecules and various crystal surfaces ({002}, {111}, and {200}) were calculated. The results revealed a strong correlation between the solvent’s ability to form hydrogen bonds and the interaction energies. Solvents with strong hydrogen bonding capabilities (carboxylic acids, esters, and ethers) exhibited the strongest non-bonded interactions, followed by those with sulfone groups and hydroxyls with weaker non-bonded interactions. Notably, sulfonates displayed the strongest binding energies, exceeding -70 kcal/mol, potentially hindering movement at the surface and influencing crystal growth. This strong binding might have explained the observed shortened growth along the c-axis, suggesting a more stable crystal configuration on this surface. The Electrostatic Potential (ESP) surface contour map revealed the electron density distribution between the solute and solvent molecules, which helped explain the observed binding energies. The correlation between the binding energy ratio of {111}/{200} and {111}/{002} crystal facets in Form II paracetamol and its growth morphology in carboxylic acid solvents suggested that a higher ratio favoured elongated scalenohedral crystals, while a lower ratio led to rod-shaped or plate-like crystals.
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