Estudo da estabilidade da melatonina e compatibilidade das formulações farmacêuticas

Melatonin (MT) is a hormone produced by the pineal gland as a product of tryptophan metabolism. Several formulations containing MT are commercially available. However, because it is considered a food supplement, there are no monographs in the Brazilian Pharmacopoeia referring to raw materials or finished products, and the requirements for registration are more flexible than those for medicines. Such a scenario reveals the need to study aspects related to the stability of this hormone and its compatibility with excipients used in the formulations. The HPLC methodology for the analysis of MT and possible degradation products was optimized and validated considering the parameters of linearity, precision, accuracy, limit of detection and quantification, selectivity, and robustness. The stability study was carried out with two active pharmaceutical ingredients from different manufacturers (APIMT1 and APIMT2). Intrinsic stability analysis showed that there was significant degradation of API under acid and basic hydrolysis, oxidation, heat exposure and photodegradation. Only in the APIMT2 samples was the formation of possible degradation products observed. A significant instability of MT under oxidation at acidic pH was observed. When evaluating the antioxidant capacity of the excipients, ascorbic acid and citric acid were the ones that showed the greatest MT protection capacity. In the evaluation of the compatibility of the formulations by Thermal Analysis, it was possible to observe and identify the melting point of MT (120.77 oC) and the characteristic event of MT degradation in all binary API-excipient mixtures (1:1), which demonstrates the compatibility. Thus, for the manufacture of MT it is important to note that the API presents degradation problems under certain stress conditions such as exposure to light, heat, oxidation, and hydrolysis; however, no excipient described for the manipulation of solid dosage forms has been shown to be incompatible. In view of the instabilities of MT under stress in liquid media, it is important to pay attention to the best packaging conditions, storage of products and pH of the formulation, and which liquid products are more susceptible to degradation compared to solid products.