Co-Processing of Amorphous Solid Dispersions via Co-precipitation

概述通过抗溶剂共沉淀制备无定形药物形式，以增加生物利用度，改善溶出度，流动性和稳定性，用于连续生产。为什么？为什么？无定形药物在体内比晶体形式更易溶解。对无定形药物形式的工业兴趣允许使用共沉淀方法。共沉淀降低了API破坏的机会，这在使用高温的HME和喷雾干燥中更常见。怎么做？最初，通过对一个模型水晶系统进行基准测试来确定仪器的范围，将允许对系统行为的理解。将使用混合速度、剪切速率、温度、流速、不同溶剂检测设备的重现性、准确度和精密度。这些数据将被用于扩展到一个良好的研究聚合物。经过初步测试后，将实现一个很好理解的聚合物-API系统。这将允许转移到尚未实现的其他聚合物-API系统的能力。在所有阶段，加工材料将通过XRPD、DSC、粒度仪、电子显微镜（固态、物理性质）进行表征。最后，Co-非晶系统预测，使用DDMAP工作包1-3的数据，我们可以预测制造稳定ASD的最佳工艺/组成选择。

Overarching scopeTo prepare drug forms in the amorphous state to increase bioavailability, improve dissolution, flowability and stability for continuous manufacturing via anti-solvent co-precipitation. Why? Amorphous pharmaceuticals are more soluble in the body than crystalline forms. Industry interest in amorphous drug forms allows for the co-precipitation method to be utilised. Co-precipitation reduces the chances of API destruction which is more common in HME and spray drying where high temperatures are used. How?Initially, scoping out the instrumentation by benchmarking against a model crystalline system will allow for an understanding of the behavior of the system. Mixing speeds, sheer rates, temperatures, flow rates, different solvents will be used to test the reproducibility, accuracy, and precision of the equipment. This data will be used to expand to a well-studied polymer. After initial testing a well understood polymer-API system will be realised. This will allow the ability to move on to other polymer-API systems that are not yet realised. At all stages, processed materials will be characterised via XRPD, DSC, particle sizers, electron microscopy (solid state, physical properties). FinallyCo-amorphous system prediction, using data from DDMAP work packages 1-3 we can predict optimal process/composition selection for manufacture of stable ASDs.