[P2-01] Multiscale model of solid state amorphization during processing of pharmaceutical materials
Processing of active pharmaceutical ingredients and excipients to reduce and control particle size involve milling and micronization which result in severe plastic deformation and fracture. The increase in free energy of the crystal during deformation can result in polymorphic transformations and amorphization and affect the physical properties of the product, including bioavailability.
In order to predict how materials properties and processing conditions affect plastic deformation and phase transitions in pharmaceutical materials we developed a multiscale model that combines electronic structure using density functional theory, large-scale molecular dynamics simulations and a phase field modeling. At the finer scale, we use DFT to predict elastic constants of the crystals and amorphous systems of interest and validate the force fields used with MD. MD simulations provide insight into the process of amorphization and enables the characterization of the difference in enthalpy between the crystal and amorphous phase and their interfacial energy, critical to describe the nucleation and growth of the amorphous phase. Finally, the materials properties from DFT and MD calculations are used to inform a phase field model that describes, self-consistently, plastic deformation, including the nucleation of crystal defects informed by dislocation dynamics, with phase transformations.
Using the multiscale model, we investigate the effect of deformation, shear, impact and particle surface roughness on the evolution of the crystallite size and the nucleation and growth of an amorphous phase in molecular crystals of interest for pharmaceutical applications.
In order to predict how materials properties and processing conditions affect plastic deformation and phase transitions in pharmaceutical materials we developed a multiscale model that combines electronic structure using density functional theory, large-scale molecular dynamics simulations and a phase field modeling. At the finer scale, we use DFT to predict elastic constants of the crystals and amorphous systems of interest and validate the force fields used with MD. MD simulations provide insight into the process of amorphization and enables the characterization of the difference in enthalpy between the crystal and amorphous phase and their interfacial energy, critical to describe the nucleation and growth of the amorphous phase. Finally, the materials properties from DFT and MD calculations are used to inform a phase field model that describes, self-consistently, plastic deformation, including the nucleation of crystal defects informed by dislocation dynamics, with phase transformations.
Using the multiscale model, we investigate the effect of deformation, shear, impact and particle surface roughness on the evolution of the crystallite size and the nucleation and growth of an amorphous phase in molecular crystals of interest for pharmaceutical applications.