Desenvolvimento e estudo de estabilidade de suspensões de sulfadiazina para uso pediátrico

Abstract

Brazil is one of the countries with the highest prevalence of congenital toxoplasmosis in the world and the treatment of the infection is done through the association of sulfadiazine (SDZ), pyrimethamine and folinic acid. However, SDZ is commercially available only astablets, which turns difficult the treatment of children. In this context, the objective of this work was to develop and to determine the stability of formulations for pediatric use, with adequate characteristics and excipients compatible with the age group. To achieve our goal, SDZ suspensions at 100 mg/mL were prepared, using the active pharmaceutical ingredient (API, suspension A) or crushed tablets (suspension B). The formulations were prepared, after careful choice of excipients and concentrations to be used and stored under refrigeration for 30 days for stability evaluation. The physical stability of the suspensions was analyzed through the organoleptic characteristics, pH, particle size and viscosity. The chemical stability was verified through the SDZ content, which was determined by an ultra-high performance liquid chromatography (UPLC) method developed and validated in this study. The dissolution of the formulations was also investigated, as well as the microbiological stability, for the latter it was necessary to inactivate the antimicrobial action of the formulation components, to avoid false-negative results. The pH of the suspensions remained in the neutrality range and unchanged during the study (p>0.05). It was observed a decrease in particle size during the study (p<0.05) for both formulations, as well as the formulation B (50,63 ± 2,65 μm) presented a significantly larger particle size than formulation A (35,2 ± 5,26 μm). Additionally, it was possible to identify the presence of crystals in suspension A, attributed to SDZ API, however, there was no change in this characteristic throughout the analysis period. Both formulations presented non-Newtonian flow and there was no statistically significant change in viscosity during 30 days. Suspensions A and B presented contents close to 100% without showing statistical variation, which proved the chemical stability of 30 days. In addition, they presented more than 80% dissolution in 15 minutes without statistically significant difference when compared to the percentage of SDZ dissolved in the beginning and at the end of the study, such as between formulations A and B. No microbial growth was observed (<10 CFU/mL) in both formulations, as well as the presence of Escherichia coli was not identified, that indicated that the developed formulations met the pharmacopeial requirements. The formulations developed in this study showed physical, chemical and microbiological stability for 30 days and may be an option for the treatment of congenital toxoplasmosis.