This work was carried out as part my Master's thesis.
This work was carried out using a combination of Visual Habit and MS Excel.
Visual Habit is outlined within this book.
Materials Studio was used to modify the molecules.
This is a brief summary of the entire thesis.
Introduction
Polymorphs are when a substance can exist in two forms, a common example is two polymorphs of carbon: Diamond and Graphite. Both only contain carbon but have different structures and different properties. Diamond is hard whilst graphite is considerably softer. Pharmaceutical drugs, such as ibuprofen, also have different polymorphs. Polymorphsism in pharmeuticals is extremly important since differnt polymorphs can have different effects. See thalidomide
Visual Habit is a soon to be commercial software developed at the University of Leeds to estimate the shape of a crystal, whether it be spherical or plate like. The software accepts molecules in the form of a .cif file. The .cif files for ibuprofen were obtained from the Cambridge Crystallographic Data Centre (CCDC) are available here.
Visual Habit produces a lattice energy alongside the crystal shape. The lattice energy is representation of the stabilty of the crystal; the more negative the value the more the stable the crystal. This lattice energy was used to determine the stabilty of the polymorphs. The software had eight different methods of calculating the lattice energy.
Aims
The main aim of this project was to understand the stability of different polymorphs of ibuprofen. The lattice energy and the crystal morphology were obtained using the computational software VisualHabit.
The project had several supplementary objectives; the first was to assess the ability of the science to accurately predict the lattice energy of a crystal. The second was to assess the accuracy of different methods when predicting the stability of the crystal. An additional objective was to identify the most ideal .cif file that ought to be used when attempting to calculate the lattice energy, since the reading were take under different conditions.
The final aim was to use software developed by CASTEP to obtain a modified version of the molecule. The software, an addon to Materials Studio, would find a "perfect" verison of the molecule; one that was not effected by external factors. Both polymorphs were to be modified and the a lattice energies of each were compared with original molecules.
Obtaining the data
The twenty molecules of ibuprofen were downloaded from the CCDC database and the lattice energies of all twenty were calculated using each forcefield(method). Some methods resulted in errors for the lattice energy and were therefore ignored in the comparison. The data is shown below.
Molecules of polymorph one are shown at top of the table, these molecules have the code IBPRAC,01,03,05,06,07,08,09,10,11,12,13,14,15,16,17,18 and 19. The modified version of the first polymorph is also included and has the name DFT1. Polymorph II only had one molecule, IBPRAC04, the modified version is DFT2.
Cell parameters, R factor (Error measurement) and lattice energies for all available molecules of ibuprofen. Molecules with high R factors are shown in red. Positive lattice energies are shown in yellow. Starred molecules were used for weighted average and standard deviation.
Results and analysis
The two polymorphs of ibuprofen had a clear difference in lattice energy, with lattice energy of polymorph one consistently having more negative lattice energy, even when the forcefield was adjusted.
Only two of the forcefields remained consistent in their estimation of the lattice energy.
The analysis of criteria for the best molecule showed that there are several main criteria for identifying the highest quality material: temperature, pressure, chirality, radiation probe and the type of sample. Low temperature and low pressure were preferable since it would mean that the location of the molecules would be more easily identifiable leading to a more accurate result. The lattice energy was more sensitive to extreme changes in pressure than temperature