Subject melting, extrapolation

When the solvent-isolated losartan was subjected to DSC characterization, the DSC curve (Fig. 3-5, curve A) showed a minor endotherm at an extrapolation onset temperature of about 229°C (10°C/min) and a major melting endotherm at an extrapolation onset temperature of about 273°C (10°C/min). When a sample of Form I was heated to 255°C and then cooled back to room temperature, the subsequent DSC curve showed only the high-temperature endotherm (Fig. 3-5, curve B). Chemical analysis (HPLC) and solution NMR showed no change in the material heated to 255°C and cooled back to room temperature. However, XRPD indicated a change in the crystal structure. Therefore, it was concluded that the minor endotherm corresponded to a kinetically irreversible enantiotropic polymorphic transition and that the losartan system was not under complete thermodynamic control. Form I is the low-temperature stable form, up to the transition point, and the high-temperature stable form was... 

After calibration, the dissociation rate is extrapolated down to low energies, and in the present situation some noteworthy non-monotonic variations are found at energies close to 140 kcal mol These variations are not spurious, but convey some strong anharmonidties in both parent and product clusters assod-ated with the occurrence of melting in this energy range. That dissodation properties relate to the thermodynamical behavior can be understood on the basis that the density of states is important to measure the available phase space open to dissociation, but is also characteristic of statistical properties at equilibrium, in particular the partition ftmction and all other canonical observables. Interestingly, the connection between dissodation properties and thermodynamic features such as phase transitions has been the subject of intense experimental and theoretical research, not only in cluster physics and chemistry, but also in nuclear physics. ... 

The melting point (T ), the highest temperature point of the melting endotherm (this not the same as the extrapolated ending point of the melting, see Fig. 2.48). To determine the melting point, the sensitivity on the DSC trace must be increased considerably so that the determination procedure will be less subjective. 

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