Phase Diagram, Tolbutamide and PEG 6000 - METTLER TOLEDO

Phase Diagram, Tolbutamide and PEG 6000

Sample

Tolbutamide and PEG 6000 as well as mixtures

Tolbutamide

PEG 6000 

Conditions

Measuring cellDSC820

Pan: Aluminum 40 µl, hermetically sealed

Sample preparation: As received or physical mixtures of both components

DSC measurement: Heating from 30 °C to 175 °C at 10 K/min

Atmosphere: Nitrogen, 50 cm3/min

 

 

 

Interpretation

Tolbutamide forms a solid dispersion with PEG 6000, but not a solid solution. In a solid solution the components form mixed crystals with a definite melting range. In this case tolbutamide and PEG 6000 form a eutectic with a composition of 30% TBA and 70% PEG 6000 with the same melting point as the PEG 6000 used.

The peak A at about 39 °C corresponds to a solid-solid transition of tolbutamide. At 60 °C peak B can be observed. Excess TBA melts (peak C) if more than 30% TBA is present.

 

Evaluation

The onset temperatures and the heats of fusion ΔH are evaluated from the melting curves.

SamplePeak APeak BPeak C
Onset / ΔH°CJ/g°CJ/g°CJ/g
TBA 100%398--12793
TBA 90%/PEG 10%39.17.453.719.8121.175
TBA 70%/PEG 30%39.35.853.251.610948
TBA 50%/PEG 50%39.43.954.393.981.622.8
TBA 30%/PEG 70%39.51.555.9138.8104.8-
TBA 10%/PEG 90%39.50.355.3166.7116.4-
PEG 100%--55178128-

 

The following phase diagram can be constructed by plotting the onset temperature against the concentration of TBA (in weight percent). The solid-solid transition of TBA occurs at about 39 °C, named here as modifications A and B. Above 54 °C, either the liquid or the solid phase B is present depending on the TBA concentration. The dotted lines are extrapolations. Additional measurements with mixtures of different composition would have to be performed in order to confirm these extrapolations and to construct a complete phase diagram.

 

 

Phase diagram for the system tolbutamide-PEG 6000

 

Conclusion

Phase diagrams of binary mixtures can be determined by DSC.

 

Phase Diagram, Tolbutamide and PEG 6000 | Thermal Analysis Application No. HB828 | Application published in METTLER TOLEDO TA Application Handbook Pharmaceuticals