Solid State Mechanical Properties of Crystalline Drugs and Excipients Subtantiate Newly Discovered Visco-Elastic Characteristics

摘要

Thermal Mechanical Analysis (TMA) of crystalline drugs and excipients in their pre-melttemperature range corroborate their newly founded linear dielectric conductivityproperties with temperature. TMA of crystalline Active Pharmacy Ingredient (API) orexcipient softens 30-100oC below the calorimetric melting phase transition.Acetophenetidin melts as measured calorimetrically (DSC) at 135oC, but softens under alow mechanical stress at 95oC. At the melting temperature the crystals cannot support theapplied load, collapse and the TMA probe moves vertically at a rapid rate. Themechanical properties yield to a soft structure and a dimensionally slow disintegrate to asharp mechanical change at the melt temperature. In order to establish a structureproperty relationship the United States Pharmacopeias (USP) melting standard drugswere evaluated by TMA, DSC and Macro-photography. The USP standard melttemperature for Vanillin (80oC), Acetophenetidin (135oC), and Caffeine (235oC) areeasily determined calorimetrically. The TMA variables include heating rate, appliedstress and sample thickness. The combined TMA, DSC, and the Macro-photographytechniques allow for a wide variety of newly discovered physical properties of Drugs andExcipients.