OptiMelt Automated Melting Point System - Stanford Research ...

Appendix A Pharmacopeia vs. Thermodynamic Melting Points 79Thermodynamic Melting PointThe transition from solid to liquid does not take place instantaneously – it requires afinite amount of time. The melting process begins at the point where the first particles ofthe bulk substance turn into the liquid state – the onset point. The end of the melt isreached when the last solid particles have gone over into the liquid phase – the clearpoint. During the entire melting process of a pure compound: (1) the temperature of thepure substance remains constant (thermodynamic melting point) while (2) heat isconstantly transferred from the heating stand to the sample and (3) the heating stand itselfexperiences a range of temperatures that depends on the selected heating rate.When determining the melting point according to the US or International Pharmacopeias,the temperature of the heating stand at the end of the melt (clear point) is read. Thatsingle temperature record depends on the temperature ramping rate, it ignores the rangebetween the start and the end of the melt and it is not the “true” thermodynamic meltingpoint of the pure compound.Temperatureat clear point(MP Pharma )Thermodynamicmelting point(MP Thermo )Temperature (T)Thermodynamiccorrection(∆T(r))OventemperatureSampletemperatureStart of melting(Onset point)End of melting(Clear point)t 0t fTimeFigure 40. Graphical representation of the thermodynamic correctionFigure 40 is a simple representation of the sequence of events that take place during themelting of a pure substance. At the start of the melting (time = t 0 ), the block and thesample are at approximately the same temperature. As soon as the melt starts the sampletemperature stabilizes while the block continues heating up. As the melt progresses, thesample remains at constant temperature (thermodynamic melting point, MP thermo ) whilethe block continues to heat up. Heat is constantly transferred from the block to the sampleat a rate that is proportional to the temperature difference between the sample and theblock. The temperature of the block at the end of the melt (time= t f ) is recorded as theOptiMelt Automated Melting Point System