Polymorphism, Tolbutamide

Sample

Tolbutamide

Application

Active ingredient (oral antidiabetic)

Conditions

Measuring cell: DSC820

Pan: Aluminum 40 µl, hermetically sealed

Sample preparation: As received, no preparation

DSC measurement: for A, B, C: Heating from 30 °C to 100 °C. Cooling from 100 °C to 30 °C. Second heating run from 30 °C to 175 °C. The sample weight was 5.057 mg.

DSC measurement: for D, E: Heating from 30 °C to 175 °C. Cooling from 175 °C to 30 °C. Second heating run from 30 °C to 175 °C. The sample weight was 4.389 mg.

The heating rate for all the steps was 10 K/min, the cooling rate was 5 K/min.

Atmosphere: Nitrogen, 50 cm³/min

Polymorphism Tolbutamide

Interpretation

Different peaks can be observed, depending on the maximum temperature reached. The first peak at about 40 °C is, however, only reversible if the sample is not heated above 100 °C. It is caused by an enantiotropic solid-solid transition. If the melting temperature is first exceeded (>140 °C) and the sample afterwards cooled down, then a new modification can be observed with a broad melting range in the second heating run. The broad peak shape indicates the presence of impurities arising from decomposition.

Evaluation

	First peak		Middle peak		Melting peak
	Onset, °C	ΔH, J/g	Onset, °C	ΔH, J/g	Onset, °C	ΔH, J/g
A Heating run 1	39.5	7.7	-	-	-	-
B Heating run 2	36.2	6.2	-	-	-	-
C Heating run 3	39.5	7.5	-	-	126.4	90.9

	First peak		Middle peak		Melting peak
	Onset, °C	ΔH, J/g	Onset, °C	ΔH, J/g	Onset, °C	ΔH, J/g
D Heating run 1	39.3	7.1	-	-	126.9	91.5
E Heating run 2	-	-	91.4	44.8	-	-

Conclusion

Different modifications of the sample are formed depending on the thermal pretreatment. The modifications can be clearly distinguished with DSC.

_{Polymorphism, Tolbutamide | Thermal Analysis Application No. HB832 | Application published in METTLER TOLEDO TA Application Handbook Pharmaceuticals}