Investigating magnetic fields for pharmaceutical processing

Bratty, Victoria Louise (2020) Investigating magnetic fields for pharmaceutical processing. PhD thesis, University of Nottingham.

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Abstract

Many pharmaceutical compounds have poor aqueous solubilities that can result in difficulties in formulation, and ineffective therapeutic treatments. Pharmaceutical compounds can exist in different states (i.e. amorphous or crystalline), as well as existing in different polymorphic forms, which can dramatically affect physicochemical properties. However, a technique called containerless processing has shown promise in the control of crystallisation and crystal form. Using high strength magnetic fields (> 16 T) that are strong enough to freely levitate pharmaceutical solutions we investigated the potential of magnetic levitation for containerless processing.

Initial experiments included the characterisation of starting materials and production of reference materials, to be used as a comparison to samples in later chapters. Initial levitation studies involved the levitation of paracetamol solutions (water/ ethanol) using our helium-cooled, closed-cycle superconducting magnet. We showed that it was possible to crystallise pharmaceutical materials whilst levitated. Form I paracetamol was predominantly formed, whilst form II was occasionally also formed showing that there could be an influence of the process on the crystal form produced. In further levitation studies we used clotrimazole, which had already been shown to form amorphous gels when levitated by acoustic levitation. Our study was therefore a comparison of acoustic and diamagnetic levitation methods. Interestingly droplets were found to produce an amorphous gel, crystalline shell, or a combination of both. Optimisation of the experimental set up with mirrors allowed filming of the droplet from the side, which allowed investigation into the crystallisation/ amorphisation processes involved. Final experiments include more detailed investigations into the influence of the magnetic field. Paracetamol, clotrimazole and propranolol were crystallised from solution under magnetic fields of 1 T. Low strength magnetic fields did not have any effect on the crystallisation of paracetamol or clotrimazole. However, propranolol crystallised under low strength magnetic fields produced form III propranolol which is not usually formed from solution, usually from a melt. It is therefore demonstrated that diamagnetic levitation offers a unique ability to investigate crystallisation/ amorphisation of different pharmaceutical drugs in solution.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Allen, Stephanie
Hill, Richard
Burley, Jonathan
Keywords: Pharmaceutical compounds, Magnetic fields
Subjects: R Medicine > RM Therapeutics. Pharmacology
Faculties/Schools: UK Campuses > Faculty of Science > School of Pharmacy
Item ID: 61377
Depositing User: Bratty, Victoria
Date Deposited: 31 Dec 2020 04:40
Last Modified: 31 Dec 2020 04:40
URI: http://eprints.nottingham.ac.uk/id/eprint/61377

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