Characterization of Drugs by DSC

Introduction

It is well known that interactions between the active substance and excipients can influence the pharmacological properties and behavior of drugs in biological systems

In this study, mixtures of excipients and piroxicam as the active substance were ground together and analyzed by DSC. The active substance, piroxicam (4-hydroxy-2-methyl-N-pyridinyl-2H-1, 2-benzothiazine-3-carboxamide 1,1-dioxide) is a non-steroidal drug that is often used for the treatment of osteoarthritis and rheumatoid arthritis. It shows a therapeutic effect in very small doses and has few side effects. The drug’s mechanism has to do with the disruption of prostaglandin formation and inhibition of the enzyme cyclo-oxygenase.

Besides the active substance itself, piroxicam tablets contain the following excipients: anhydrous lactose, lactose monohydrate, microcrystalline cellulose type 102 and magnesium stearate.

Experimental Details 

Measuring cell: DSC821e ,

Crucible: aluminum 40 µl, lid with 50-µm hole to produce a self-generated atmosphere

DSC program: heating from 75 to 200 °C at 2 K/min

Atmosphere: stationary air

Measurements and Results 

The mixture of excipients and the active substance were first measured separately. The excipients curve shows a melting peak at 140 °C, while the active substance (piroxicam) melts at 202 °C (Fig. 1).

A series of mixtures was then prepared by finely grinding the mixture of excipients with increasing amounts of piroxicam. Figure 2 displays the DSC curves of some of these samples.

The mixtures show an endothermic effect just below 200 °C. This is attributed to the melting of the active substance. The fact that the melting temperature is lower (up to 10 K) can only be explained by assuming that there is a non-eutectic interaction between the substance and the excipients. The nonlinear increase in surface area is also evidence supporting an interaction (Fig. 3).

Conclusions

The DSC curves show that interactions occur between the different constituents, both in the samples obtained by grinding the active substance with the excipients and in the piroxicam tablet itself. The interactions become less and less important with piroxicam contents greater than 60%.

Once the nonlinear relationship between the enthalpy of melting and the content of the active substance has been established, the DSC piroxicam peak area can be used to calculate the content of the active substance for quality control purposes.

_{Characterization of Drugs by DSC | Thermal Analysis Application No. UC 162 | Application published in METTLER TOLEDO Thermal Analysis UserCom 16}