PhD Studentship - Analysis of Polar Drug Molecules and Excipients by Ultrahigh Performance Supercri
Within the pharmaceutical industry, an evolution in the types of molecules being developed is underway. There is a move from drugable molecules based on Lipinski’s ‘Rule of Five’ classification to those that no longer fit this traditional approach. There are three notable trends emerging in terms of molecular (and formulation) design:
- Molecules with very low or very high hydrophobicity (Log P) that enable facile penetration through physiological membranes or increased residence time at site of action
- A move towards larger and more complex biomolecular entities, e.g. oligonucleotides, peptides, mAbs etc.
- Development of complex formulations and vehicles for drug delivery such as liposomes, polymer nanoparticles and drug-polymer conjugates.
These new drug types pose different chromatographic challenges that are often not resolvable via traditional approaches such as reversed-phase HPLC, ion chromatography (IC) or size exclusion chromatography (SEC).
Recent advances in SFC have opened the way to selective identification, characterisation, and quantification of polar compounds. SFC has also demonstrated its applicability in for the analysis of polymers commonly used as excipients. In addition to MS detection, orthogonal detectors, e.g. ELSD, CLND and CAD can be added to aid detection and quantification of non-chromophoric materials. UHPSFC offers an additional, or alternative approach to analysis of some of these new drug molecules where reversed-phase chromatographic approaches can be challenging.
To realise the full potential of this instrumentation the development of robust new UHPSFC methodologies will be required, e.g. Understanding the changes in MS ionisation response, eluent flow split ratio, ion suppression issues, in addition to low level detection, quantification and calibration with different detectors requires exploration.
The project is funded for 4 years and welcomes applicants from the UK and EU who have or expect to obtain at least an upper second class degree in chemistry or allied subjects/relevant disciplines. Funding will cover fees and a stipend at current research council rates (201718 and subject to increase in 201819) of £ 14,553 per annum.
Due to funding restrictions this position is only open to UK/EU applicants.
Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified