NMR/MRI studies of drug diffusion in polymer melts

固体药物分散体(SDDS)越来越多地被选为一种制剂策略，旨在克服通常与难溶化合物相关的低口服生物利用度。SDDS的制备方法有多种，包括热熔融挤出法、HME法。生产性能稳定的无定形挤压产品的关键挑战是需要确保挤压后没有残留的结晶药物，并且产品具有高药物含量均一性。了解最终产品行为的关键参数之一是能够测量(并最终预测)药物在高温下在液体中的自扩散系数的真实值(Dself)。我们最近展示了使用多核脉冲梯度(PFG)核磁共振测量药物在HME温度下的自扩散是可能的，这让我们对热熔融挤出过程中原料药的动力学和质量传输行为有了新的见解。博士课程将涉及对热熔体挤出的所有方面的详细研究，并将包括建立一个高温核磁共振兼容的池来研究药物在聚合物熔体中的扩散。除了研究原料药，通常通过使用19F核磁共振，我们还试图利用2H核磁共振和13C核磁共振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.