Research projects
Current research projects undertaken by the Pharmaceutical Science Research Group include:
Analysis and control of morphological forms
The pharmaceutical industry often uses a milling process to control particle size and to mix powders into a homogenous blend so that a uniform product is formed.
However, the challenge with milling is that it forces particle surfaces to change from a crystalline to an amorphous form. This can be problematic, as different morphological forms have different rates of dissolution and bioavailability. Understanding the effects of processing on powders is important, particularly for pharmaceutical applications.
By preparing different forms and subjecting them to a range of environments, the transition between forms can be monitored and explained, to minimise the over-milling of a product.
Computational modelling of transdermal drug delivery
Many medicinal compounds cannot be delivered orally because they are degraded in the intestine or by the liver, are poorly absorbed, or irritate the gastrointestinal tract. In such cases, transdermal delivery may be considered. However, skin is not uniform between genders, age, race, or even on the same person. A model membrane is often used to minimise these differences, although experimentally this is still time-consuming.
The use of computational analysis to compare existing data between human skin and model membranes not only shows how effective a given model membrane is, but can also explain why some small molecules can cross the skin barrier more easily than others. It can also explain the mechanism behind permeation.
In a related research area, data from the water/octanol partition coefficient, expressed in the form log P, has been used to predict the capability of organic molecules to transfer across membranes. Our interest in this and other physicochemical model systems covers measurement methods, limitations of the log P model, alternatives to log P and its use in prediction through the quantitative structure-activity relationship (QSAR) analyses.
In particular, we are looking at how measurements involving the water/octanol system can shed light on biologically important solvation and de-solvation processes. The aim is to investigate the transfer of small organic molecules, not only from aqueous solution to membranes, but also to other hydrophobic environments such as “hydrophobic” binding sites on proteins.
Excipients by design
The Pharmaceutical Science Research Group is working on the synthesis of novel polymers for use as excipients and of synthetic modification of naturally occurring polymers, for use in drug delivery.
Examples include novel approaches to the synthesis and physicochemical characterisation of dendrimers, nanoparticles and SMART microgel polymers. Research includes investigations into the stability of technologically important colloidal and particulate formulations, e.g. metered dose inhalers.
New analytical techniques for the pharmaceutical industry
This area of research involves the development and use of pectrophotometric and calorimetric techniques for pharmaceutical materials analysis, including drug stability testing, excipient compatibility, chemical stability of foodstuffs and agrochemicals, and the biophysical characterisation of vesicle systems, nucleic acids and synthetic polymeric surfactants.
Intelligent active-release delivery systems
Microgels are discrete colloidal particles, or "micro-sponges", that respond to changes in their environmental conditions, such as temperature, pH and electrolyte. This sensitivity can be controlled by careful selection of monomers and co-monomers.
These micro-sponges shrink and swell in direct response to how favourable they find their environment. This expansion and contraction finds potential for delivery devices, absorbing and releasing enclosed materials through their porous network.
These micro-devices can also be attached to a substrate such as cotton, to make a wound dressing capable of the controlled release of an incorporated active.
Supercritical fluid-based processing
Supercritical fluids offer considerable promise as processing media for the formation of microparticles of drugs and pharmaceutical excipients. There are two main reasons for using this technique. Firstly, the selective solvating power of supercritical fluids makes it possible to separate a particular component from a multi-component mixture. Secondly, the favourable mass transfer properties and high solubility of solvent in supercritical fluid make the formation of the microparticles rapid and efficient.
Supercritical fluids also offer a number of other advantages, such as use of organic solvents, high temperatures, high sheer stresses can be avoided which can therefore aid in the effective, safe and green processing of APIs and pharmaceutical excipients. Solubility behaviour of supercritical fluid can be altered or tuned by the fine adjustment of pressure and temperature. Supercritical fluids can also be utilised as a solute and can help in the depression of melting point or glass transition temperature of an excipient, allowing microparticle production at far lower temperatures.
Research focuses on the processing of excipients and APIs with supercritical CO2 and utilisation of this approach in the development of novel drug delivery systems (NDDS). We are particularly interested in the “safe” formulation of NDDS for biologics for oral delivery which also entails incorporation of bio-molecules and proteins into inorganic host materials. Immobilisation of biologics on a solid surface improves their thermal and chemical stability. These biologics on an inorganic host can then be safely coated with lipids and/or other suitable excipient using supercritical fluid processing. This approach can provide sustained, targeted and safe passage to a drug to the lower intestine where it can be released and absorbed.
Research interests also include the development of novel inorganic materials as well as preparation of nanoparticles using green technologies i.e. supercritical fluid technology and microwave synthesis.
Hot melt extrusion technology (HME)
Development of solid dosage forms via HME (solubility enhancement, taste masking – oral disintegrating tablets, ODTs).
Metabonomics
Professor Jeremy Everett’s research covers metabonomics, lead generation for drug discovery and molecular structure elucidation. He has 79 publications and patents including two recent, landmark publications in PNAS and Nature on the discovery of pharmacometabonomics.
Paediatric medicines
Professor Steve Wicks’ research has focused on the application of the biophysical sciences to the design and commercialisation of pharmaceutical products. This work matches the biophysical characteristics of active pharmaceutical ingredients to innovative formulation designs that result in the optimal expression of pharmacology.