A method for the characterisation of amorphous complex mixtures
The analysis of mixtures is critical for the pharmaceutical industry as it is a requirement for quality controls. More specifically, amorphous solid dispersions (ASD) are key in the development of new drugs as they have shown to improve their solubility and bioavailability. As the amorphous substance is often the active pharmaceutical ingredient (API) of the drug, the availability of methods for the analysis of amorphous components is essential. Current methods include mass spectroscopy, nuclear magnetic resonance and infrared spectroscopy; however, the quantification of ASDs for formulation purposes remains a challenge and no method is currently available to measure the level of crystallinity of an API.
Researchers at Oxford have created a new and robust method that enables not only the characterisation of the single components of a complex mixture but also the level of crystallinity of the sample. Among the numerous advantages, the method is also applicable to alternative experimental datasets such as NMR, thus increasing the versatility of the method in the analysis of amorphous samples.
Amorphous components in complex formulations
The analysis of mixtures is of particular interest in the development of pharmaceuticals due to regulations and quality control requirements. Although there are a number of techniques currently available for this purpose, the characterisation of amorphous components in complex formulations remains a challenge.
Amorphous solid dispersions (ASDs) comprise an amorphous active pharmaceutical ingredient (API) dispersed in a water-soluble polymer binder. They are commonly used to improve the solubility and bioavailability of the API, making them key in the development of pharmaceuticals. Due to the amorphous nature of ASDs, their stability is poorly understood with re-crystallisation of the API being the most likely cause of a formulation decomposing. In reality, ASDs often contain the API in both amorphous and crystalline form.
As the amorphous API is essential to the function of the drug, methods for its characterisation and quantification within the complex formulation are essential. ASDs are currently studied through mass spectroscopy, nuclear magnetic resonance and infrared spectroscopy; however, such techniques struggle to quantify ASDs for formulation purposes and are limited in determining the crystallinity of the API in the ASD.
Novel algorithm for scattering data analysis: characterisation of APIs
Academics at Oxford have tackled such limitation and developed a general and robust method for the characterisation of APIs in complex formulations. The technology relies on diffraction experiments performed on complex mixtures and uses an algorithm to extract the resulting scattering data from each component’s contribution.
The new method allows:
- the structural characterisation of an amorphous API in the mixture
- the quantification and monitoring of the crystallinity, which makes possible:
– the determination of the maximum API loading level capable of inhibiting crystallisation
– the identification of drug design strategies for improving stability of the amorphous form
Advantages of the algorithm includes:
- ease of use
- versatility as it can be applied to other experimental datasets including spectroscopy data
- computationally inexpensive
- This same methodology is readily transferable to the study of other complex mixtures beyond those mentioned, such as battery materials, heterogeneous catalysts, and liquid fuels.
Oxford University Innovation Ltd. has filed an international patent application (PCT) on the technology (WO 2019/180430A1) and welcomes discussions with companies interested in licensing it for commercial development.
about this technology