Desenvolvimento de método analítico, estudos de estabilidade e avaliação da qualidade de formas farmacêuticas líquidas orais contendo hidroxiureia

Abstract

Sickle cell disease (SCD) is a syndrome belonging to the hemoglobinopathies group that is among the most prevalent worldwide. It has significant relevance for public health in Brazil, especially in Bahia. This condition is mainly characterized by the deformation of red blood cells into a sickle shape, resulting from genetic alterations caused by the predominance of hemoglobin S (HbS). It is an inherited disease that predominantly affects the black population (both black and brown individuals). Several therapeutic protocols have been adopted for its treatment, focusing on the pharmacological approach. In this context, hydroxyurea (HU), a chemotherapeutic agent, is recommended as the only drug capable of alleviating clinical symptoms and improving the quality of life of patients with SCD. However, despite its relevance for SCD treatment and other myeloproliferative disorders, HU lacks a stability-indicating analytical method (SIAM) for the active pharmaceutical ingredient or pharmaceutical forms described in the 6th edition of the Brazilian Pharmacopoeia or other official compendia. Given this gap, the objective of this work was to develop and validate a SIAM, as well as to conduct stability studies on the HU molecule. Additionally, oral liquid formulations containing HU prepared in three pharmacies in Salvador, Bahia, were evaluated. HU was subjected to forced degradation studies under acidic, basic, neutral, oxidative, and thermal conditions. The developed method employed reversed-phase High-Performance Liquid Chromatography (HPLC) with a photodiode array detector (PDA). Separation was performed using a Phenomenex® C8 column (250 x 4.6 mm, 5 µm), maintained at 25 °C. The method optimization included a mobile phase composed of water and ethanol (97:03, v/v) in isocratic mode, with a flow rate of 0.5 mL/min, injection volume of 20 µL, and detection wavelength of 214 nm. Following degradation guidelines, HU degraded significantly under all tested conditions. A degradation product (DP), identified as hydroxylamine (HA), exhibited a retention time of approximately 5.16 minutes and a resolution greater than 2 compared to the main peak, demonstrating spectral purity. The results confirmed that the proposed method is stability-indicating. The evaluation of the manipulated formulations revealed a high sanitary risk for patients using HU.