Inverse Gas Chromatography

Transcription

1 Inverse Gas Chromatography David R.Merrifield Presentation to iprd Industrialists Club Weetwood Hall, 26 th November 2010.

2 Inverse Gas Chromatography What is it? - with respect to chromatography? Chromatography - IUPAC definition = a physical method of separation in which the components to be separated are distributed between two phases, one of which is stationary, while the other moves in a definite direction. Gas and gas / liquid separation uses a known and usually commercial (solid) stationary phase on which unknown (liquid) analytes are separated for the purposes of identification and / or quantification. Inverse Gas Chromatography literally inverts this!

3 Comparison with conventional Gas Chromatography Now we are interested in the column!! Gas Chromatography Active substrates are used as stationary phases on which analytes of interest are retained and separated. Samples are stable, volatile organic materials. Stationary phases of suitable polarity are used to achieve the separation. Used for qualitative analysis, separation and identification. Inverse Gas Chromatography The principle is inverted, the analyte of interest is used as the stationary phase. Organic liquids are used as probes to judge the affinity (polarity) of the surface. The objective is to determine the polarity of the analyte (stationary phase). Can be run at different relative humidities.

4 Description of IGC as configured in the Surface Measurement Systems IGC 2000 IGC is based on a conventional Gas Chromatograph (Agilent). Mass flow controllers to provide a stream of humidified carrier gas. Column oven. Detection by FID and TCD. PC controlled Operational and Analysis software. Uses non-polar (alkanes) and polar probes to assess surface characteristics. Measures net retention time and from this a surface energy plot can be constructed.

5 Dispersive Surface Energy Dispersive Component of Surface Energy g d s Sequential injection of alkanes with increasing C-chain length at fixed concentration. Plot RTlnV N vs. a(g d L) 1/2 then g d s = (slope/2n A ) 2 Surface Measurement Systems Ltd

6 Interpreting Inverse Gas Chromatography What does the technique tell us? The work of adhesion can be separated into two component, that due to the liquid and that due to the solid. The slope of the alkane line is given by 2 N.a.γ sd, therefore we can evaluate γ sd - the surface energetic of the solid. When polar probes are injected (EtOH, CHCl 3, ethyl acetate, 1,4-dioxane etc.) their points sit above the alkane line, the vertical distance from the line representing ΔG SP0.

7 Applications of Inverse Gas Chromatography Why does the technique help us? Application area Relevance Polymers and composites Papers and inks, toners Pharmaceuticals Abrasives Confectionery Environmental Physical strength, adhesion Adsorption, choice of fillers Wettability, adhesion. Suitability of fillers, wear resistance Surface properties of chocolates. Adsorptive vs. Absorptive properties

8 Development of Inverse Gas Chromatography History of relevance to pharmaceutical industry. Dorris and Gray, Schultz and Lavielle et al, developed uses of IGC in the mid 1980s for polymers, composites, measurements of adhesion. Ticehurst, York et al applied IGC to pharmaceutical contexts in 1994 (M.Ticehurst, PhD, University of Bradford). A component part of an EPSRC funded Tripartite Research Programme Development of a commercial igc instrument, the SMS igc 2000, arising from a pharmaceutical consortium, G.Buckton, D.R.Williams et al, Relevance as a technique for PAT, Process Analytical Testing? SMS re-launch IGC as Surface Energy Analyzer, SEA, Nov 2009.

9 Potential use of IGC for pharmaceuticals Surface energetic is a possible cause of batch to batch variability for Active Pharmaceutical Ingredients. Probably equally applicable to non-active excipients. Possible cause of differences in: Wettability of batches. In-vitro dissolution rate. Drug excipient interactions Adhesive cohesive interactions in powder systems such as inhalable formulations (drug lactose blends)

10 IGC my interests Unanswered questions! Does the technique have the sensitivity, and thus capability, to really judge differences between batches? Or between samples of drug substance prepared from different routes / solvents? How sensitive is it to process related changes? Is it sensitive enough to detect face specific differences (ie. related to the chemical composition of specific crystal faces)? Can this be clarified and rationalised by molecular modelling?