Thermal analysis can be used to determine shelf-life and kinetic parameters in pharmaceutical systems. This work investigates the kinetic of lumefantrine thermal decomposition, an antimalarial, using non-isothermal and isothermal experimental data. The non-isothermal conditions are analyzed applying Vyazovkin method, while isothermal conditions employ models fitting procedure and artificial neural network. Lumefantrine was characterized by powder X-ray diffraction and Fourier transform infrared spectroscopy. The initial stage of lumefantrine thermal decomposition, about 5% of conversion, corresponds to the loss of chlorine and hydroxyl, being correctly predicted by the neural network as a complex event. At room temperature, the D3 model is appropriate to describe the process, once the half-life time is 19 months, in agreement with manufacturer. Isoconversional model determined the activation energy along the whole process while isothermal methodology determined the global value considering the entire process. The results provide important information for the pharmaceutical industry to assay levels of acceptable lumefantrine contents.

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Thalidomide was indicated as a sedative and antiemetic and prescribed for pregnant women. Its tragic teratogenic effects culminated in withdrawal from the market. Since the discovery of its anti-angiogenic and anti-inflammatory actions, thalidomide has been used in the treatment of leprosy and multiple myeloma, which justify studies of its stability. We investigated the effects of irradiation of thalidomide up to 100 kGy (fourfold the usual sterilizing dose for pharmaceutics). The β polymorph of thalidomide was obtained in an isothermal experiment at 270 °C. All samples underwent gamma irradiation for specific times. At different doses, decomposition of the pharmaceutical was not observed up to 100 kGy. The observed effect was angle turning between the phthalimide and glutarimide rings modulated by repulsion towards the carbonyl group, leading to a stable energetic configuration, as measured by the equilibrium in the torsion angle after irradiation. The thalidomide molecule has a center of symmetry, so a full turn starting from 57.3° will lead to an identical molecule. Further irradiation will start the process again. Samples irradiated at 30 and 100 kGy have more compact unit cells and a lower volume, which leads to an increase in the intermolecular hydrogen interaction within the unit cell, resulting in higher thermal stability for polymorph α.

A general kinetic equation to simulate differential scanning calorimetry (DSC) data was employed along this work. Random noises are used to generate a thousand data, which are considered to evaluate the performance of Levenberg-Marquardt (LM) and a Hopfield neural network (HNN) based algorithm in the fitting process. The HNN-based algorithm showed better results for two different initial conditions: exact and approximated values. After this statistical analysis, DSC experimental data at three heating rates for losartan potassium, an antihypertensive drug, was adjusted by the HNN method using different initial conditions to obtain the activation energy and frequency factor. Additionally, it was possible to recover the parameters for the kinetic model with accuracy, showing that the conversion is described by a complex process, once these values do not correspond to any ideal models described in the literature.

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