(478g) Alpha and Beta Glycine Nanocrystal Growth and Dissolution Kinetics in the Presence of an Electric Field through Molecular Dynamics - Towards Electric Field Controlled Crystallization
- Conference: AIChE Annual Meeting
- Year: 2016
- Proceeding: 2016 AIChE Annual Meeting
- Group: Computational Molecular Science and Engineering Forum
Wednesday, November 16, 2016 - 10:00am-10:15am
Control of crystal polymorphs is of significant interest in the field of drug discovery and development. An active pharmaceutical ingredient (API) can exhibit different crystal forms, which in turn determine its solid-state stability, bioavailability, dissolution rate, as well as other key solid-state characteristics. It is well known that while a particular polymorph may be more thermodynamically stable, its rate of formation (kinetics) may be slower relative to its metastable counterpart. Consequently, a pharmaceutical crystallization process that has been designed to produce only the desired stable polymorph may result in different, or worse yet, undiscovered, polymorphic forms, due to unforeseen variations in the manufacturing process conditions. It is therefore essential to not only understand, but also control, the mechanisms of polymorph formation. This includes understanding of not only the competitive nucleation and growth process, but also dissolution as one attempts to selectively dissolve potentially unwanted polymorphs in favor of the desired forms. Ultimately, this mechanistic understanding must translate to quantitative estimates to be used in design and control models. Recent advancements of ultrafast laser physics have shown that intense, pulsed laser is highly effective in manipulating various molecular states in the non-resonant regime. Specifically, several experiments have illustrated the effect of continuous wave (CW) as well as pulsed laser in a crystallization system. These include accelerated crystallization of urea, crystallization of glycine in undersaturated solution, and glycine polymorph selection. As the atomic forces due to the application of an external field can be represented classically via Lorentz Law in the molecular Hamiltonian, electric field controlled crystallization presents the tantalizing possibility of placing the experimentalist in direct control of the underlying free energy surface upon which the crystallization process is taking place. This manipulation of free energy barriers will manifest itself in nucleation, growth, and dissolution electric field dependent rates. As a step further towards electric field controlled crystallization, we seek to determine, using molecular dynamics (MD), first principle, and polymorph specific, dissolution and growth rates for various electric field intensities. We believe this to be an important step towards the ultimate goal, which is expressing the growth, and dissolution, rates as functions of the applied electric field.