Manufacturing and characterising mixed micro- and nanoparticle formulations for personalised dosage

The aging population gives rise to questions regarding how best to formulate medicines for geriatric patients. Many patients are prescribed more than 5 medications and are often required to take in excess of 15 tablets a day; so called polypharmacy. Often these patients are elderly and may struggle to follow complex medication regimens due to a combination of health issues. A possible technological solution is to 'dial-in' a dosage specific to the patient using a formulation that would contain multiple actives with extended release profiles. To prevent actives adversely interacting within the formulation we seek to encapsulate the actives within polymeric nano- and microparticles. Using concepts of continuous manufacturing and microfluidic technology we can control particle size and active release profiles. We need to demonstrate improved understanding of drug-particle and particle-particle interactions to design better performing formulations. Additionally, and in conjunction with STEaPP, we seek to investigate the regulatory and societal barriers to developing and implementing multi-drug formulations (polypills). This PhD will demonstrate the state-of-the-art technological solutions to improving patient outcomes when faced with multi-morbidity, while identifying approaches to obtain regulatory approval and patient uptake. .
Background
To achieve a `dial-in' personalised dosage formulation we propose to use a polyparticle capsule concept. The polyparticles will be produced using microfluidic processing and formulated to produce capsules containing particles with differing actives. We will use the full suite of physico-chemical characterisation techniques to assess the particles and their interactions with each other and the final capsule. We will also assess the release profiles of the actives which we can control by means of particle size and composition. Previously we demonstrated the potential of mass spectrometry analysis to characterise microparticles, for example in the development of a polymer microparticle system designed to deliver a protease inhibitor.1,2 In that work, ToFSIMS was used to identify a biphasic core-shell polymer particle as well as the variation in distribution of the active agent for differing compositions. This concept will be applied to assess the polymer and active compositions of the micro/nano-particles produced for this project. For de-convoluting complex organic systems including polymers, proteins and biological agents the potential of the 3D OrbiSIMS instrument will be utilised. Further benefits of the 3D OrbiSIMS such as the lateral resolving power of <100 nm will allow an unprecedented insight into the surface chemistry of the micro/nano-particles. This concept affords control over a number of dosages for different agents utilising a `gumball' style dial-a-dosage tailored therapy..
Brief workplan
Nano/micro-particle manufacture via microfluidics
Characterisation of nano/micro-particles using techniques such as 3D OrbiSIMS
Development of polyparticle capsules and subsequent release analysis
Throughout the PhD issues related to regulatory approval and patient compliance will be explored and disseminated through a chapter/publication on technology adoption and uptake.