Kinetics of Lumefantrine Thermal Decomposition Employing Isoconversional Models and Artificial Neural Network

Abstract

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.

Thermal Stability Kinetics and Shelf Life Estimation of the Redox-Active Therapeutic and Mimic of Superoxide Dismutase Enzyme, Mn(III) meso-Tetrakis(N-ethylpyridinium-2-yl)porphyrin Chloride (MnTE-2-PyPCl5, BMX-010)

“…Isothermal decomposition of solids generally occurs at the product-reagent interface [ 44 ], being described by kinetic models well established in the literature [ 48 – 50 ]. These models correlate the decomposition fraction, α ( t ), with time at chosen appropriate temperatures.…”

“…Isothermal TG Data. The MLP neural network applied in this study was proposed initially by Sebastião et al [48][49][50]. The architecture of this MLP has only one artificial neuron in the input and output layers.…”

“…Network. Isothermal decomposition of solids generally occurs at the product-reagent interface [44], being described by kinetic models well established in the literature [48][49][50].…”

“…We describe herein the first study on the kinetics of thermal degradation of MnP-based redox-active therapeutics under isothermal and nonisothermal conditions. Additionally, it is worth noting that thermal decomposition kinetic models were evaluated using a state-of-the-art approach, based on the multilayer perceptron (MLP) artificial neural network [48][49][50][51][52]. MnTE-2-PyPCl 5 was chosen as a representative API of the class of Mn(III) 2-N-alkylpyridylporphyrins, currently developed as SOD mimics, biomimetic models, catalytic antioxidants, and redoxactive therapeutics.…”

Thermal Stability of Amorphous Solid Dispersions

“…Thermal stability of different classes of drugs such as anti-cancer [ 47 ], vitamin [ 48 ], antimalarial [ 49 ], antihypertensive [ 50 ], antibiotic [ 51 ], and anti-HIV drugs [ 52 ] was widely evaluated in the literature by the proposed CKA approach using thermal analysis techniques ( Table 2 ) The studies on kinetics, as well as mechanism of thermal decomposition of drugs have important theoretical significance to obtain information on the thermal stability of drugs, and further understanding of the relationship between thermal stability and molecular structure.…”