The role of modulated temperature differential scanning calorimetry in the characterisation of a drug molecule exhibiting polymorphic and glass forming tendencies.
The thermal properties of the drug sulfapyridine were studied using a combination of differential scanning calorimetry (DSC), modulated temperature differential scanning calorimetry (MTDSC) and thermo optical analysis with a view to examining the combined use of these methods as a characterisation strategy. Conventional DSC indicated that quenched sulfapyridine exhibited a series of transitions on reheating at 10 degrees C min(-1) which were ascribed to a glass transition (56.9 degrees C), cold crystallisation (103.7 degrees C), a solid-solid transition (131.4 degrees C) and metastable and stable polymorphic melting (177.3 and 186.3 degrees C). MTDSC studies were able to show the glass transition with much greater clarity in the reversing signal than was possible using the conventional technique, while it was also possible to observe the phase angle which again allowed clearer visualisation of the Tg. Thermooptical analysis confirmed the interpretation of the DSC and MTDSC data, showing the formation of spherulitic crystals which converted to a needle-shaped morphology on heating, these being ascribed to metastable and stable polymorphs respectively. The study has therefore demonstrated that using the three techniques in combination allows unique insights into the glass transitional and polymorphic behaviour of a drug substance.
Bottom
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Mettler Toledo Ltd, Boston Road, Leicester, UK. rod.bottom@mt.com
D002152:Calorimetry, Differential Scanning / Q000379:methods*; D003460:Crystallization; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013237:Stereoisomerism; D013427:Sulfapyridine / Q000737:chemistry; D013696:Temperature
D004364:Pharmaceutical Preparations; D013427:Sulfapyridine