Solid-state Mechanical Properties of Crystalline Drugs and Excipients
Journal of Thermal Analysis and Calorimetry
Thermal mechanical analysis (TMA) of crystalline drugs and excipients in their pre-melt temperature range performed in this study corroborate their newly found linear dielectric conductivity properties with temperature. TMA of crystalline active pharmacy ingredients (APIs) or excipients shows softening at 30–100 °C below the calorimetric melting phase transition, which is also observed by dielectric analysis (DEA). Acetophenetidin melts at 135 °C as measured calorimetrically by DSC, but softens under a low mechanical stress at 95 °C. At this pre-melting temperature, the crystals collapse under the applied load, and the TMA probe shows rapid displacement. The mechanical properties yield a softening structure and cause a dimensionally slow disintegration resulting in a sharp dimensional change at the melting point. In order to incorporate these findings into a structure–property relationship, several United States Pharmacopeia (USP) melting-point standard drugs were evaluated by TMA, DSC, and DEA, and compared to the USP standard melt temperatures. The USP standard melt temperature for vanillin (80 °C) , acetophenetidin (135 °C) , and caffeine (235 °C)  are easily verified calorimetrically via DSC. The combined thermal analysis techniques allow for a wide variety of the newly discovered physical properties of drugs and excipients.
Thakur, S.; Maheswaram, M.; Mantheni, D.; Kaza, L.; Perara, I.; Ball, D.; Moran, J.; Riga, A. Solid-state mechanical properties of crystalline drugs and excipients. Journal of Thermal Analysis and Calorimetry 2012, 108, 283-287.
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