Linkam's new automated temperature-controlled stage microscopy-based analytical technique

A new, streamlined hot stage microscopy-based analytical technique has successfully been used to screen the miscibility of drug-polymer combinations. This technique, thermal analysis by structural characterization (TASC), simplifies the route to screening and understanding sample properties.

Researchers at the University of East Anglia (UEA) used TASC in conjunction with a Linkam MDSG600 heating-cooling automated XY stage, mounted on a Linkam Imaging Station equipped with reflective LED light source and a 10x magnification objective. This thermo-optometric setup was used with Linkam’s data analysis software to identify the melting point depression and post-melting dissolution of particles of model drug, felodipine, which were screened over spin-coated thin films of ten of the most commonly used pharmaceutical polymers.

Polymers are widely used to enhance in vivo dissolution and absorption of active pharmaceutical ingredients (APIs), – and drug-polymer miscibility is a critical factor for success in early formulation. A range of experimental characterization techniques, most commonly differential scanning calorimetry (DSC), and theoretical calculations, have traditionally been used to assess drug-polymer miscibility. However, the methodology is complex, time-consuming and requires relatively large amounts of material. New research from UEA is set to improve and simplify this methodology by using TASC to detect melting point depression of the drug-induced by the added polymer. This key phase transition was able to be detected significantly faster (20-40 times) than the conventional DSC method, with no loss of sensitivity. Importantly, the quantity of the material required is approximately 1/1000th of that used in a normal DSC experiment.

Duncan Stacey, Sales and Marketing Director, Linkam Scientific Instruments comments: “This new method of structural characterization looks to be a valuable alternative to established methodology. TASC is a conventional light microscopy-based method that detects changes in images automatically. It does this by comparing a sequence of images pixel by pixel, so it can focus on very specific local changes, from microscopic regions to large-area phase changes. The resulting image series of the samples captured during thermal treatment (either heating, cooling or an isothermal hold) is taken and the TASC algorithm quantifies the changes of surface features in successive micrographs of samples, giving instant accurate graphical representation of these structural changes which can be plotted against temperature or time.”

One of the researchers, Sheng Qi, School of Pharmacy, University of East Anglia explained: “To successfully formulate a so-called solid dispersion product, the drug needs to be highly miscible with the polymer. However, the pre-formulation stage of screening suitable polymers is often a lengthy process requiring the use of a range semi-empirical, theoretical and experimental methods. The results from this study demonstrate TASC as a promising screening tool for rapidly selecting the polymeric excipients for pharmaceutical formulations development.”

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