Co-Processing of Amorphous Solid Dispersions via Co-precipitation

在非晶态下制备药物形态，以提高生物利用度、改善溶出度、流动性和稳定性，以通过反溶剂共沉淀进行连续生产。为什么？无定形药物在体内比晶体形式的药物更易溶解。业界对无定形药物形式的兴趣使共沉淀法得以利用。共沉淀减少了原料药破坏的机会，这在使用高温的HME和喷雾干燥中更为常见。如何？最初，通过对照模型晶体系统进行基准测试来确定仪器的范围将允许理解系统的行为。将使用混合速度、剪切速率、温度、流速、不同的溶剂来测试设备的重复性、准确性和精密度。这些数据将被用来扩展到研究得很好的聚合物。经过初步测试后，将实现一个易于理解的聚合物-原料药系统。这将允许转移到其他尚未实现的聚合物-原料药系统。在所有阶段，将通过XRPD、DSC、粒度仪、电子显微镜(固态、物理性能)对加工材料进行表征。最后，Co-非晶系预测，使用DDMAP工作包1-3的数据，我们可以预测制造稳定的ASD的最佳工艺/成分选择。

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.