Understanding process effects on the stability of amorphous form products (recrystallization of amorphous form products)

目的：该项目的目的是了解不同工艺如何影响药物输送无定形产品的稳定性，以限制它们的再结晶。这些目标大致可分为三个方面：通过两种不同的路线制备并储存在一系列条件下的模型药物输送系统的特性识别影响模型系统稳定性的关键分子因素(例如实验设计)开发更通用的预测模型和分子指纹。方法：药物输送系统的特性是该项目的关键方面。电子显微镜和X射线衍射等技术将被用来识别非晶态中的纳米晶区，这些晶区可能会引发材料的重组，从而导致产品不稳定。这将允许确定尺寸、形貌和结构，从而允许对样品中的晶区进行温度-空间评估。这一过程不仅依赖于时间，而且还受到用于产生无定形形式的配方和工艺的类型的影响。一旦开发出可靠的方法，就可以建立与来自不同生产方法的样品的相关性。该项目还将研究根据表征开发的模拟和模型，因为它们可以在测试之前用于预测配方特性。用已建立的数据建立预测模型，将对预测活性成分和药物输送系统的结晶至关重要。潜在影响：该项目的影响将在需要无定形产品的领域，例如医药中的许多药物。在这种情况下，如果产品不稳定，并结晶，这可能会影响疗效。在开发识别、理解和最终预测这种结晶的方法时，我们将能够考虑加工和储存条件的影响。

Aims:The aim of the project is to understand how various processes influence the stability of drug delivery amorphous form products, in order to limit their recrystallisation. These objectives could roughly be divided into three aspects: Characterisation of model drug delivery systems, prepared via two different routes, and stored in a range of conditionsIdentification of the key molecular factors that affect the stability of the model systems (e.g. designing of experiments)Development of more general predictive models and molecular fingerprints.Methodology:Characterisation of the drug delivery systems is the key aspect of the project. Techniques such as electron microscopy and X-ray diffraction will be used to identify nano-sized crystalline regions within the amorphous state that may initiate re-structuring of the material, and thus lead to product instability. This will allow determination of the size, morphology and structure allowing a tempero-spatial assessment of crystalline areas within the sample. Not only is this process time-dependent but is affected by the type of formulation and processes used to generate the amorphous form. Once reliable methods are developed, a correlation with samples that are developed from different production methods can be developed. The project will also look at simulations and models developed from the characterisation, as they can be utilised to predict formulation properties prior to testing. Predictive models with the established data, would be crucial for predicting the crystallisation of active ingredients and drug delivery systems. Potential Impact: The impact of this project will be in areas where an amorphous product is desired, such as with many drugs within medicine. In this instance, if the products are unstable, and crystallise, this may affect the efficacy. In developing methods to identify, then understand and ultimately predict this crystallisation, we will be able to consider the effects of processing and storage conditions.