Clear Raw Material Identification (RMID) Using DSC

Clear Raw Material Identification (RMID) Using DSC

Raw material identification or incoming goods inspection is of paramount importance for the quality and safety of drug products, wherever chemical substances are used in the pharmaceutical industry – maybe as an educt of chemical reactions or as a basis for further processing.

Raw material identification or incoming goods inspection is of paramount importance for the quality and safety of drug products, wherever chemical substances are used in the pharmaceutical industry – maybe as an educt of chemical reactions or as a basis for further processing.

Characteristic quantities which are suitable for being used for substance identification are

  • Melting/transition temperature
  • Melting enthalpy (heat of fusion)
  • Transition enthalpy
  • Glass transition temperature
  • Specific heat capacity

All of them can be determined by means of differential scanning calorimetry (DSC).

The melting temperature and melting enthalpy are typical for crystalline substances including polymorphs; the glass transition temperature is an attribute of amorphous materials. Semi-crystalline substances exhibit both melting and glass transition effects.

 Characteristic Data of Phenacetin

Phenacetin was introduced in 1887 as an analgesic, but because of its harmful, especially kidney-damaging effect in combination with other pain medication, this pharmaceutical is for most countries no longer available on the market as a drug product. Pure phenacetin is, however, part of the thermal analysis purity set from NIST (National Institutes of Standards and Technology, SRM 1514) and therefore well suitable for illustrating the melting point determination.

In the following experiment, 1.04 mg of phenacetin was heated in a nitrogen atmosphere in aluminum crucibles at a heating rate of 10 K/min to 160°C. The DSC curve (fig. 1), arising from that measurement, shows an endothermal effect which represents melting of the substance.

USP Chapter <891> recommends to correlate the extrapolated onset temperature of the DSC effect (in the present case at 134.5°C) to the melting point of the crystalline material. The term for that is the melt onset temperature. The corresponding melting enthalpy (or heat of fusion) is calculated by peak integration resulting in 159.6 J/g. Evaluation can be automatically run using the AutoEvaluation functionality of the NETZSCH Proteus® software.

Both results agree well with the values given in literature (1) and (2).

Fig. 1: DSC measurement on phenacetin (measurement conditions see text) If the measurement is carried out at 20 K/min, one heating step just needs about 7 minutes to be finished

Literature:
(1)  H. Manzo, A.A. Ahumada,, J. Pharm. Sci., 1990, 79, 12, pp 1109 – 1115 (407.2 K)
(2) A. Pen͂a, B. Excalera, A. Reillo, A.B. Sánchez, P. Bustamante, J. Pharm. Sci., 2009, 98, 3, pp 1129 – 1135 (28.75 kJ/mol, based on a molar mass of 179.21 g/mol)

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