Framework for Rational Amorphous API Development

在这个项目中，将通过确定分子结构、工艺历史和杂质对相关原料药化合物的局部结构、稳定性和性能的影响来探索非晶代景观。为了了解不同的加工路线如何有利于理想的结果，将研究加工和隔离路线对非晶固体形成和稳定性的影响。该项目将重点关注的主要目标包括：1。选择初始API候选物进行研究。将每种原料药通过选定的加工链，包括结晶，喷雾干燥，熔体淬火，ASD配方。3 .探索非晶态固体生成后的分离和干燥阶段，以确定它们对最终API稳定性的影响，并制定优化它们的新策略（重点了解动态干燥曲线对Tg和溶剂塑化的影响）。样品将使用相关技术进行表征，包括光学、热、光谱、衍射/散射和/或机械测试，以确定非晶样品结构的一致性或可变性，作为加工路线的功能。样品还将经受应力/加速稳定性条件，以评估物理稳定性和变化/再结晶作为关键应力条件（如T， %RH，水环境和机械）的函数。

In this project the amorphous generation landscape will be explored by determining the impact of molecular structure, process history and impurities on the local structure, stability, and performance of relevant API compounds.To understand how different processing routes can favour desirable outcomes, the influence of processing and isolation routes on the ease of amorphous solid formation and stability will be investigated.The project will focus on key objectives including:1. Selection of initial API candidates to study.2. Take each API through a selected processing chain to include crystallisation, spray drying, melt quenching, ASD formulation.3. Explore the isolation and drying stages following amorphous solids generation to determine their impact on the final API stability and develop new strategies for optimising them (focus on understanding the impact of dynamic drying profiles with respect to Tg and on solvent plasticisation).4. Samples will be characterised using relevant techniques including optical, thermal, spectroscopic, diffraction/scattering and/or mechanical tests to identify consistency or variability in amorphous sample structure as a function of the processing route. Samples will also be subjected to stress//accelerated stability conditions to assess physical stability and changes/re-crystallisation as a function of key stress conditions (such as T, %RH, aqueous environments and mechanical).