Thermal Stability Investigation and the Kinetic Study of Folnak® Degradation Process Under Nonisothermal Conditions

Abstract

The nonisothermal degradation process of Folnak drug samples was investigated by simultaneous thermogravimetric and differential thermal analysis in the temperature range from an ambient one up to 810 degrees C. It was established that the degradation proceeds through the five degradation stages (designated as I, II, III, IV, and V), which include: the dehydration (I), the melting process of excipients (II), as well as the decomposition of folic acid (III), corn starch (IV), and saccharose (V), respectively. It was established that the presented excipients show a different behavior from that of the pure materials. During degradation, all excipients increase their thermal stability, and some kind of solid-solid and/or solid-gas interaction occurs. The kinetic parameters and reaction mechanism for the folic acid decomposition were established using different calculation procedures. It was concluded that the folic acid decomposition mechanism cannot be explained by the simple reaction order (ROn) model (n = 1) but with the complex reaction mechanism which includes the higher reaction orders (RO, n > 1), with average value of <n > = 1.91. The isothermal predictions of the third (III) degradation stage of Folnak sample, at four different temperatures (T (iso) = 180 degrees C, 200 degrees C, 220 degrees C, and 260 degrees C), were established. It was concluded that the shapes of the isothermal conversion curves at lower temperatures (180-200 degrees C) were similar, whereas became more complex with further temperature increase due to the pterin and p-amino benzoic acid decomposition behavior, which brings the additional complexity in the overall folic acid decomposition process.