The morphology of a crystal grown in a solvent can change depending on the solvent used during the crystallization process. Modification of the morphology of a crystal can be engineered based on information conferred by the functional groups of the facets of interest and the functional groups of the solvent. This study aims to predict the effect of the alcoholic functional group of amyl alcohol, benzyl alcohol, and phenol on the {002}, {011}, and {110} facets of Form I paracetamol. Prediction and simulation studies were carried out using an embedded tool available in Material Studio. The interaction between the solvents (phenol, benzyl alcohol, and amyl alcohol) and the surfaces used in this study revealed that the {011} facet had the most negative nonbonded energy, followed by the {110} and {002} facets. Overall, the nonbonded interactions between the solvents and the facets were dominated by Coulombic interactions, accounting for more than 90% of the energies, which is within the range from −2566 to −3613 kcal/mol. The binding energy for amyl and benzyl alcohols on the facets of the crystal, ranked from the strongest to the weakest, was in the order {002} > {110} > {011}, while for phenol, the rank was {002} > {011} > {110}. This result is in line with the observed crystal morphology of Form I paracetamol crystallized in a polar protic solvent, in which the most favorable solvent binding on the {002} facets delayed the growth of the elongated hexagonal morphology along the c-axis and formed prismatic-like morphology. Using benzyl alcohol as a case study, an assessment of synthon formation on facets {002} and {011} showed that synthon B is an important synthon for the growth of units of these facets, while synthon F is an important building block synthon for the {110} facet.
The modification of crystal shapes is used intensively in designing particles with desired properties to ensure the efficiency of the manufacturing processes. In this work, urea crystals grew in various polar protic solvents by cooling crystallization that produced α-form urea. The aspect ratios of the crystals were found to be in the range from 14.77 to 1.44, grown in the following solvents: water > methanol > ethanol > isopentanol > isobutanol > pentanol > butanol > propanol > isopropanol. An attempt to establish a correlation between the nonbonded energy, solvent molecule size, binding energy, and the change in morphology revealed that the aforementioned factors could not accurately predict the aspect ratios of the urea crystals. The solvent-surface binding energy showed the {111} and {001} capping facets recorded the highest strength (most negative energy), while the {110} facet was the lowest. The inhibition of the solvent molecules on the {001} and polar {111} facets stopped the growth along the c-axis by stopping the formation of synthon A and synthon B, while the growth along the a-axis was halted by stopping the formation of synthon B. The transformation from elongated cuboid to prismoidal shape of urea was governed by the {111}/{110} energy ratio, i.e., it must be <1.78.
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.
Succinic acid is a potential co-former to produce co-crystal, thus an understanding of the dissolution behaviour of succinic acid crystal is crucial for designing the co-crystal. In this works, α-succinic acid was chosen as a model compound for this study regardless its attractive crystal chemistry and its diverse surface properties. The aims of this study are to analyse the morphology of succinic acid crystal (form A) and to analyse the dissolution behaviour of succinic acid crystal (form A) in the ethanol solution using molecular dynamic simulation. Prediction of form A succinic acid morphology were conducted with different combination of charge set and potential function i.e ESP and CVFF which produces hexagonal needle-like shape morphology and shows good agreement with the experimental crystal shape. Dissolution of α-succinic acid in ethanol solvent was investigated using dynamic simulation. Visual observation and mobility assessment shows that the molecules at the edge of the crystal tends to dissolve faster compared to the molecules at other position on the facet.
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