Enhanced Solid-State NMR of Amorphous Solid Dispersion in Pharmaceutical Sciences

Lead Research Organisation: University of Liverpool
Department Name: Chemistry

Abstract

Pharmaceutical drugs have two key components: the Active Pharmaceutical Ingredients (API) and the excipient. The API is the part of the drug that produces the expected response or effect, whereas the excipient is usually chemically inactive but helps bind the drug together and allows the drug to be classed as biologically safe. To obtain the desired criteria for an API, both the pharmacodynamic and pharmacokinetic factors must be considered along with the therapeutic effect of the drug. The formulation of the drug is often thought of as the most stable form for therapeutic use and is crystalline but this state impacts the drugs mode of action in the body - its' bioavailability.
Of particular interest are the family of APIs in Class II drugs due to their weak water solubility, which results in poor bioavailability and directly corresponds to lower drug absorption. In cases such as this, the solid crystalline form of the API is converted to the solid amorphous form. This process is desirable due to the increased solubility without alteration of the chemical structure. The pure amorphous form of an API has a much higher energy than that of a crystalline API and so less energy is required for solvation. Despite this advantage, the pure amorphous API does tend to be unstable and so often returns to the thermodynamically more stable crystalline state. To prevent this from happening, more stable forms of amorphous API including amorphous solid dispersion (ASD) have been investigated.
ASDs are usually binary systems made from a polymeric carrier (polymer) as the excipient and the API. The polymeric carrier is key not only to the stability of the drug but also to the absorption and dissolution rates. As the process from crystalline to amorphous is not thermodynamically favourable, extra energy is required for this conversion using processing techniques such as melt extrusion, bead coating and spray drying resulting in a stable ASD. Amongst many physical and chemical characteristics, the key to the stability of ASD is the API-polymer mixing.

Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy is a very powerful technique used to determine chemical structure and dynamical behaviour of solids at the atomic scale, and understand spatial proximities in mixtures. This project will primarily focus on exploiting the capabilities of NMR spectroscopy to develop a deeper understanding of the stability of API in ASD for its use in pharmaceutical sciences to improve the bioavailability in APIs. The work will build on advanced NMR approaches and previous knowledge allowing for a further understanding and exploration of ASD stability to be carried out and resulting in improved dissolution of pharmaceutical drugs in vivo.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/T517975/1 01/10/2020 30/09/2025
2599498 Studentship EP/T517975/1 01/10/2021 30/06/2025 Chanel Cooper