NMR/MRI studies of drug diffusion in polymer melts

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Solid drug dispersions (SDDs) are increasingly being selected as a formulation strategy aimed at overcoming the low oral bioavailability typically associated with poorly soluble compounds. SDDs can be prepared by a number of methods including hot melt extrusion HME. The key challenges in producing an amorphous extruded product that performs consistently are the need to ensure that no residual crystalline drug remains after extrusion and that the product has a high drug content-uniformity.One of the key parameters in understanding the behviour of the final product is to be able to measure (and ultimately predict) a true value for the self-diffusion coefficient of the drug in the liquid phase at high temperatures (Dself). We have recently shown it is possible to measure drug self-diffusion at HME temperatures using multi-nuclear pulsed field gradient (PFG) nuclear magnetic resonance giving us new insights into the dynamics and mass transport behaviour of APIs during hot melt extrusion processes.The Ph.D. programme will involve a detailed study of all aspects of hot melt extrusion and will include building a high temperature NMR compatible cell to study drug diffusion in polymer melts. In addition to studying the API, typically by the use of 19F NMR, we also seek to exploit the use of 2H NMR and 13C NMR to study the dynamics of the polymer system itself.