NMR/MRI studies of drug diffusion in polymer melts

固体药物分散体（SDD）越来越多地被选择作为旨在克服通常与难溶性化合物相关的低口服生物利用度的制剂策略。喷雾干燥分散剂可以通过许多方法制备，包括热熔融挤出HME。生产性能一致的无定形挤出产品的关键挑战是需要确保挤出后没有残留的结晶药物残留，并且产品具有高的药物含量均匀性。（并最终预测）高温下液相中药物的自扩散系数（Dself）的真实值。我们最近表明，可以使用多核脉冲场梯度（PFG）核磁共振测量HME温度下的药物自扩散，这为我们提供了对热熔挤出过程中API动力学和质量传输行为的新见解。博士该计划将涉及热熔挤出的各个方面的详细研究，并将包括建立一个高温核磁共振兼容的细胞，研究药物在聚合物熔体中的扩散。除了研究API（通常通过使用19 F NMR）之外，我们还寻求利用2 H NMR和13 C NMR来研究聚合物体系本身的动力学。

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.