What is Drug-Excipient Compatibility?

Medicine is not a single active ingredient but a mixture of the active ingredient with different excipients. In a tablet for example, excipients are used to improve the appearance and taste of the final product, to prevent the tablet from sticking to the punching tool, or to help it dissolve as soon as it is wet, etc.  

Many excipients are pharmacologically inert. However, physical and chemical interactions between the active ingredient and excipients can affect the stability, safety and therapeutic efficacy of the drug. In this case, the term drug-excipient incompatibility is used. On the contrary, if the excipient does not affect the active ingredient, both substances are compatible.  

First information about compatibility of the active ingredient and excipient is obtained by means of thermal analysis methods:

  You will find an example for a compatibility study with DSC and with TGA.

Example: Drug-Excipient Compatibility with DSC

DSC measurements were carried out with the DSC 204 F1 Nevio on:

  • Diclofenac sodium (drug)
  • Magnesium stearate (excipient)
  • Physical mixture of both (weight ratio: 1:1)

Diclofenac sodium (blue curve): The peak at 280.6°C (onset) results from melting of diclofenac. Decomposition occurs immediately after melting (exothermal effect).

Magnesium stearate (orange curve): The endothermal effect with 3 maxima at 76.0°C, 89.1°C and 114.9°C is due partly to melting of the sample and partly to evaporation of surface and bound water.

Mixture diclofenac sodium + magnesium stearate (green curve): The peak of magnesium stearate is detected. However, melting and decomposition of diclofenac are shifted to lower temperatures. This indicates an interaction between the drug and excipient.

--> Hint for possible incompatibility

DSC measurements on diclofenac sodium (blue curve), magnesium stearate (orange curve) and on the mixture (1:1) of both (green curve)

Example: Drug-Excipient Incompatibility with TGA

TGA measurements were carried out with the TG 209 F1 Nevio on: 

  • Diclofenac sodium (drug)
  • Magnesium stearate (excipient)
  • Physical mixture of both (weight ratio: 1:1)

Diclofenac sodium (blue curve): The sample begins losing mass at 303.1°C. This indicates the decomposition of diclofenac.  

Magnesium stearate (orange curve): The mass loss of 3.9% is due to the release of surface and bound water. The decomposition begins at 351°C.

Mixture of diclofenac sodium + magnesium stearate (green curve): Evaporation of the water present in magnesium stearate occurs in the same temperature range. However, decomposition of the mixture begins at lower temperature (279°C) than with the single components. This indicates an interaction between the drug and excipient.

--> Hint for incompatibility

TGA measurements on diclofenac sodium (blue curve), magnesium stearate (orange curve) and on the mixture (1:1) of both (green curve)

Related Methods

DSCTGA