Monash Ionic Liquids Group

Current Research interests

In recent reports, much focus has been placed on the development of a novel class of API’s, namely pharmaceutical co-crystals. Such development of novel API’s is much encouraged by the high value of the compounds and the possibility of legal protection in the form of patent coverage. Indeed, the regulatory approved classes of API’s currently consist of an amorphous form and several crystalline states that are recognised as distinct including polymorphs, salts, stoichiometric solvates, molecular complexes and recently, pharmaceutical co-crystals. Generally, the crystalline phase is preferred in APIs due to thermodynamic stability and ease of isolation, however problems arise due to solubility difficulties and polymorphism. One method to improve the solubility and stability of an API is the production of a suitable salt derivative. Numerous acids and bases with varying chemico-physico properties are utilised for this task, with an estimated half of all API’s administered as salts. Additionally, amorphous solids are being actively pursued in order to improve solubility in some cases. Amorphous materials are further from equilibrium than crystalline materials, possess higher energy states and as such exhibit faster dissolution rates and kinetic solubilities. Remarkably, identification and subsequent utilisation of API salts that are molten at room temperature, i.e. ionic liquids (ILs), does not appear to have been the focus of attention in the literature until now. In my present study the formation of a Ionic Liquid forms of known therapeutics is being pursued.  This new form of the API consists of an IL comprising an API component which is either a cation or an anion, and a counterion component which is selected from the generally regarded as safe (GRAS) list, ie is a non-toxic, pharmaceutically acceptable compound. These ‘Drug Ionic Liquids’ expectantly offer distinctly different properties to the standard crystalline salt forms of the API’s currently available, including improved solubility and/or rate of solubilisation. This makes it possible for a given API to be administered or applied through different administration/application by selection of a counterion that is appropriate for tailoring the physicochemical properties to a desired administration route.

Sponsors

Publications

Previous Academic Work

• Department of Chemistry, UCT
  Department of Pharmacology, University of Stellenbosch (US)      
  Masters Course
  2003-2004
  
  The MSc degree involved a research project followed by a dissertation entitled: “Structural and thermal characterisation of NSAIDs and cyclodextrin-NSAID complexes”. This work was supervised under the auspices of Prof. Mino Caira
  
  Results:
  Three novel crystalline forms involving Celecoxib, Rofecoxib and permethylated b-cyclodextrin were obtained and characterised.
  Several inclusion complexes involving TRIMEB, b- and g-cyclodextrin were identified and elucidated.
• Department of Chemistry, UCT
  Honours Course
  08/ 2002 – 11/2002
  
  The Honours course entailed coursework, mini research projects and a thesis following a three-month project entitled: “Synthesis and chiral molecular recognition studies of a chiral resorcinarene host”.
  
  Results:
  A unique tetrasubstituted stereoisomer of tetratosylresorcinarene was synthesised in 40% yield via modification of the upper rim of the resorcinarene using the chiral electrophile (S)-a-methylbenzyl isocyanate. This isomer was subsequently fully characterised and found to include methanol, acetonitrile and dichloromethane. Additionally a novel functionalised urea was obtained via a side reaction of the functionalised resorcinarene with excess amine.
• Department of Biochemistry, UCT
  BSc Course
  08/ 2001 – 10/2001

  Majoring in biochemistry required a two month research project entitled: “The Accumulation of a Phytoalexin in the UPS1 Arabidopsis thaliana Mutant”

Short-term Contracts

• University of the Orange Free State
  Department of Chemistry
  09/2005 – 10/2005
  Visiting Researcher
  Experiment: Recrystallisation, data collection, solving and refinement of organometallic complexes such as; trans-carbonylchlororbis(tri-m-tolylphosphino)rhodium(I) and [CpFe(PR3)(CO)(COMe)]; R=(p-tol); (p-F-Ph)
• Department of Chemistry, UCT
  07/2002 – 08/2002
  Lab Assistant
  Experiment: Studied host guest complexation of t-butyl calixarene and various hosts.
• Department of Biochemistry, UCT
  06/2001 – 07/2001
  Lab Assistant
  Experiment: Studied the conformational change of certain oligos (DNA), under different ionic concentrations.