Dsc measurement of pharmaceuticals

TA no.79 DSC Measurement of Pharmaceuticals
2007.9
－Crystal polymorphism and crystallinity －
In this brief, we measure Carbamazepine, an an- Differential scanning calorimetry (DSC) has been tiepileptic drug, and ursodeoxycholic acid, a chol- added as a general testing method to the Japanese eretic drug, to ascertain the differences of crystal Pharmacopoeia and is widely used to evaluate the thermophysical properties of pharmaceuticals. It is known that the organic compounds that com- pose pharmaceuticals can have different crystalline In one measurement, Carbamazepine, which has forms or different crystallinity due to refinement or different crystalline forms (Form I and III), and its milling. It is very important to clearly identify these hydrate were measured. In another measurement, differences when developing pharmaceuticals be- ursodeoxycholic acid was measured under three cause crystal polymorphs and crystallinity influence different milling conditions (no milling, milled 5 min, medicinal effects and formulation stability. Crystal polymorphism and crystallinity are influenced by The measurements were performed using the temperature change so DSC is indispensable in un- DSC6220 differential scanning calorimeter. derstanding the thermophysical properties of phar- For the measurements, a 2mg sample was heated at a rate of 10 °C/ min in a nitrogen atmosphere. Copyright Hitachi High-Tech Science Corporation All rights reserved. The milled samples showed an exothermic peak at around 110 °C. The milling process likely broke Figure 1 shows the DSC results for the three con- down the crystal structure of the ursodeoxycholic ditions of Carbamazepine. All samples showed a acid and changed it to an amorphous form, which was sharp endothermic peak at around 190 °C. From the Form III results, we can see that there was The longer the sample was milled, the larger the exothermic peak. The longer milling time likely in- The Form I sample showed an endothermic and an creased the proportion of the amorphous elements. exothermic peak between 170 °C and 180 °C. The crystal structure of Form I crystals melts and then DSC was used to measure the pharmaceuticals recrystallizes into the stable Form III. Carbamazepine and ursodeoxycholic acid. The re- The hydrate sample showed an endothermic peak sults confirmed the presence of crystal polymorphism due to crystal water desorption at around 80 °C. in Carbamazepine, as well as the polymorphic tran- This sample is likely crystal water adhered to Form sition temperature. For ursodeoxycholic acid, the III crystals. After dehydration, the Form III crystals results confirmed that the influence of milling on crystallinity is dependent on milling time. Using the measurements described in this brief, DSC can be used to investigate the processing and Figure 2 shows the DSC results for the three con- ditions of ursodeoxycholic acid. All samples showed a sharp endothermic peak around 200 °C, which indicates the melting of ursodeoxycholic acid. Figure 2. DSC results for ursodeoxycholic acid Copyright Hitachi High-Tech Science Corporation All rights reserved.

Source: http://www.siint.co.jp/en/documents/technology/thermal_analysis/application_TA_079e.pdf