Enhanced Solid-State NMR of Amorphous Solid Dispersion in Pharmaceutical Sciences

药物有两个关键成分：活性药物成分（API）和赋形剂。原料药是药物中产生预期反应或效果的部分，而赋形剂通常具有化学活性，但有助于将药物结合在一起，并使药物被归类为生物安全。为了获得原料药的理想标准，必须考虑药物的药效学和药代动力学因素以及药物的治疗效果。药物的配方通常被认为是治疗用的最稳定的形式，并且是结晶的，但这种状态会影响药物在体内的作用模式——它的生物利用度。特别令人感兴趣的是二类药物中的原料药家族，因为它们的水溶性较弱，这导致生物利用度差，直接对应于较低的药物吸收。在这种情况下，原料药的固体结晶形式转化为固体非晶形式。由于在不改变化学结构的情况下增加了溶解度，这种方法是可取的。原料药的纯无定形具有比结晶原料药高得多的能量，因此溶剂化所需的能量更少。尽管有这样的优势，纯无定形原料药往往是不稳定的，因此经常返回到热力学上更稳定的结晶状态。为了防止这种情况发生，人们研究了更稳定的非晶原料药，包括非晶固体分散体（ASD）。asd通常是由聚合物载体（聚合物）作为赋形剂和原料药组成的二元体系。聚合物载体不仅对药物的稳定性至关重要，而且对药物的吸收和溶出也至关重要。由于从晶体到非晶态的过程在热力学上并不有利，因此需要额外的能量来进行这种转换，使用诸如熔体挤压、珠状涂层和喷雾干燥等加工技术，从而产生稳定的ASD。在许多物理和化学特性中，ASD稳定性的关键是api -聚合物的混合。固体核磁共振（NMR）光谱是一种非常强大的技术，用于确定固体在原子尺度上的化学结构和动力学行为，并了解混合物的空间邻近性。该项目将主要集中于利用核磁共振波谱的能力，以深入了解ASD中原料药的稳定性，并将其用于制药科学，以提高原料药的生物利用度。这项工作将建立在先进的核磁共振方法和先前的知识基础上，从而进一步了解和探索ASD的稳定性，并改善药物在体内的溶解。

Pharmaceutical drugs have two key components: the Active Pharmaceutical Ingredients (API) and the excipient. The API is the part of the drug that produces the expected response or effect, whereas the excipient is usually chemically inactive but helps bind the drug together and allows the drug to be classed as biologically safe. To obtain the desired criteria for an API, both the pharmacodynamic and pharmacokinetic factors must be considered along with the therapeutic effect of the drug. The formulation of the drug is often thought of as the most stable form for therapeutic use and is crystalline but this state impacts the drugs mode of action in the body - its' bioavailability. Of particular interest are the family of APIs in Class II drugs due to their weak water solubility, which results in poor bioavailability and directly corresponds to lower drug absorption. In cases such as this, the solid crystalline form of the API is converted to the solid amorphous form. This process is desirable due to the increased solubility without alteration of the chemical structure. The pure amorphous form of an API has a much higher energy than that of a crystalline API and so less energy is required for solvation. Despite this advantage, the pure amorphous API does tend to be unstable and so often returns to the thermodynamically more stable crystalline state. To prevent this from happening, more stable forms of amorphous API including amorphous solid dispersion (ASD) have been investigated.ASDs are usually binary systems made from a polymeric carrier (polymer) as the excipient and the API. The polymeric carrier is key not only to the stability of the drug but also to the absorption and dissolution rates. As the process from crystalline to amorphous is not thermodynamically favourable, extra energy is required for this conversion using processing techniques such as melt extrusion, bead coating and spray drying resulting in a stable ASD. Amongst many physical and chemical characteristics, the key to the stability of ASD is the API-polymer mixing. Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy is a very powerful technique used to determine chemical structure and dynamical behaviour of solids at the atomic scale, and understand spatial proximities in mixtures. This project will primarily focus on exploiting the capabilities of NMR spectroscopy to develop a deeper understanding of the stability of API in ASD for its use in pharmaceutical sciences to improve the bioavailability in APIs. The work will build on advanced NMR approaches and previous knowledge allowing for a further understanding and exploration of ASD stability to be carried out and resulting in improved dissolution of pharmaceutical drugs in vivo.