Estudo termoanalítico de compatibilidade fármaco-excipiente e de estabilidade entre ácido lipóico e adjuvantes tecnológicos

Abstract

Lipoic acid (LA) is an endogenous and exogenous-occurring antioxidant that acts as an essent ial cofactor in four mult ienzymat ic complexes: α-ketoglutarate dehydrogenase, pyruvate dehydrogenase, α-ketoacid dehydrogenase and the glycine decarboxylase complex. Four therapeutic properties of this molecule have been widely studied: the ability to chelate metal ions such as Cd2+, Fe3+, Cu2+ and Zn2+, retain reactive oxygen species (ROS), regenerate endogenous antioxidants such as glutathione, besides participation in the repair of other antioxidant systems. The literature reports that LA showed promising results both in preclinical and clinical trials for the treatment of diseases such as arteriosclerosis, heavy metal poisoning, diabetes, among other neurodegenerative diseases. Thus, based on the therapeutic potential, our aim was to perform a physicochemical characterization and develop a study of drug-excipient compatibility, aiming at the rational development of a pharmaceutical product. The thermal behavior of lipoic acid was evaluated by differential scanning calorimetry (DSC) and thermogravimetry (TG), and its characterization was performed by scanning electron microscopy (SEM), X-ray diffraction (XRD) and FTIR spectroscopy. Initially a characterization study of physico-chemical properties of commercial batches of raw material was performed with various analytical techniques such as thermal analysis, scanning electron microscopy, FTIR spectroscopy and X-ray diffraction. A pre-formulation study was conducted to evaluate the compatibility of lipoic acid with pharmaceutical excipients, and a prototype formulation for a solid dosage form of lipoic acid has been proposed. Based on the results obtained, it was possible to characterize LA as a crystalline solid with uneven shapes and sizes and low melting point. The compatibility study showed that LA is incompatible with the following excipients: lactose, magnesium stearate and polyvinyl pyrrolidone (PVPK30).

A formulation with compatible excipients was prepared and then its stability was evaluated and compared to the drug by isothermal kinetic methods. The results of the stability study were quite promising, in which the developed formulation preserved the physicochemical

characteristics and increased the stability of LA. Considering these results, we can conclude that the knowledge of the physico-chemical properties of lipoic acid in different commercial batches allow the rational use of this drug during the development of new products, in order to ensure a new formulation with the quality control and stabilit y parameters well-defined, and thus complement drug therapies for various diseases for which is indicated.