Fast Scan Differential Scanning Calorimetry Distinguishes Melting, Melting-Degradation/Sublimation and Thermal Stability of Drugs

Abstract

Abstract In order to establish a structure and property (melting and oxidative or thermal degradation, or both) relationship for a United States Pharmacopeias (USP) set of standard drugs, they were evaluated by fast scan differential scanning calorimetry. A critical problem in characterizing the endothermic melting of a drug is to determine the melting range and if a chemical melts and immediately degrades. The stability of standard drugs is based on a comparison of their thermal properties at widely varying ramp or heating rates from 10 to 100°C/min. A stable crystalline drug has an obvious melting endotherm followed by a stable baseline. An unstable crystalline drug melts and immediately degrades as viewed by a shifting melt endotherm with heating rate. The USP thermally stable standards evaluated in this study include vanillin (melt temperature, Tm, 80.4°C), acetanilide (Tm, 114°C), acetophenetidin (Tm, 135°C), sulfanilamide (Tm, 165°C), sulfapyridine (Tm, 191°C), and caffeine (Tm, 235°C and Tsublimation, <220°C). In addition to the USP samples a number of commercial and model drugs, like benzoic acid (Tm, 122°C and Tsublimation, <120°C), lidocaine.HCl and procaine.HCl were also examined. Their melt profiles were ranked as stable or unstable post fusion by the fast scan DSC technique and are reported.