Drug substance differential scanning calorimetry

The photostability of two polymorphs of nicardipine hydrochloride have been studied using a number of techniques [95]. After irradiation, the drug substance decomposes to a pyridine derivative, and the photodegradation of the /1-form exceeded that of the x-form. It was also found that the color of the two different forms differed with the polymorphic state, but that grinding the two forms lessened the difference in their photochemistries. A correlation between the heat of fusion (measured by differential scanning calorimetry) and the photodegradation rate constant was observed. 

It was recognized quite some time ago that DTA analysis could be used to deduce the compatibility between a drug substance and its excipients in a formulation. The effect of lubricants on performance was as problematic then as it is now, and DTA proved to be a powerful method in the evaluation of possible incompatibilities. Jacobson and Reier used DTA to study the interaction between various penicillins and stearic acid [17]. For instance, the addition of 5% stearic acid to sodium oxacillin monohydrate completely obliterated the thermal events associated with the antibiotic. Since that time, many workers employed DTA analysis in the study of drug-excipient interactions, although the DTA method has been largely replaced by differential scanning calorimetry technology. 

Investigations for the occurrence of polymorphism have been undertaken by ir spectroscopy, differential scanning calorimetry and x-ray powder diffraction (Guinier-de Wolff). No polymorphism has been observed so far. An amorphous form may be prepared artificially by rapid evaporation of a methanolic solution of the drug substance. 

Differential scanning calorimetry cannot be applied to quantify the purity of the drug substance for the reasons mentioned in 2.31 and 2.34. However, it may be valuable in qualitative comparisons from sample to sample or batch to batch on the basis of their corresponding differential scanning calorimetry patterns. 

NIRA provides a non-destructive alternative to differential scanning calorimetry for the determination of polymorphic forms of drugs, e.g. the polymorphic forms of caffeine. NIRA has also been used to determine optical purity. While the pure opposite enantiomers of a substance have identical NIR spectra, mixing two... 

Differential scanning calorimetry is a technique that has recently been used for the detection of photodegradation products in solid drug substances. Even minor amounts of degradation product within a crystal lattice can provoke a significant decrease in its melting point. This method has successfully been used to monitor the photostability of nifedipine (15). 

Another simple identification determination of a drug substance is the melting point. A more sophisticated technique is differential scanning calorimetry (Fig. 1). The melting characteristic may be used for identification and is especially suitable for a polymorphic system. The existence of one or more polymorph forms can be identified. For the identification of hydrates or solvates, thermal gravimetric analysis (TGA) is used (Fig. 2). 

Thermoanalytical techniques have had a major application in the understanding of transitions in the skin and of drug penetration of the skin. The application of thermoanalytical techniques to prosthetics and implants is also discussed, as are recent DSC investigations of the oesophagus that provided the information on thermal stability required for successful stent implantation. The use of thermoanalytical techniques such as modulated temperature differential scanning calorimetry (MTDSC) has been be used to characterise polymeric material in order to determine whether there are interactions with drug substances to control and predict drug delivery. 

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