Thermal decomposition of active pharmaceutical substances and accuracy of the related kinetic predictions: The case of nifedipine

Abstract

Non-isothermal thermogravimetry was used to study the thermal decomposition of the nifedipine drug. The dominant process of thermal molecular degradation (as confirmed by Raman spectroscopy) starts very slowly at ∼ 150 °C, which is below the melting point of Tm ≈ 170 °C. The decomposition kinetics was described in terms of the autocatalytic Šesták-Berggren kinetics; a novel approach denoted as single-curve multivariate kinetic analysis (sc-MKA) was used to determine the following set of parameters: activation energy of decomposition Ed = 115.5 ± 2.4 kJ mol-1, decomposition pre-exponential factor log(Ad/s-1) ≈ 8.5–8.9, Šesták-Berggren kinetic exponents M ≈ 0–0.2 and N ≈ 0.3–0.5. The consequent kinetic predictions based on these results have confirmed the good thermal stability of nifedipine, which allows for the melt-quenching preparation of the amorphous phase as well as for the processing via hot melt extrusion and 3D printing. An in-depth analysis of the relevant performance of the sc-MKA approach was done based on the akin literature data for indomethacin, nimesulide, and griseofulvin. The comparison has revealed more than sufficient performance of the sc-MKA method with regard to its application to the thermal decomposition data of active pharmaceutical substances. The most critical aspect of the sc-MKA procedure was demonstrated to be the accurate determination of the model-free parameters (activation energy Ed and pre-exponential factor Ad) and their temperature trends. Considering the specificity of the sc-MKA method, i.e., the fixed value of Ed(T), the determination of the temperature dependence of Ad(T) is of utmost importance and worth extensive repeatability checks.