Dapsona: validação de métodos analíticos para formulações padronizadas na forma farmacêutica cápsula

Abstract

Dapsone (diaminodiphenylsulfone) is a synthetic antimicrobial sulfone that has been used in the treatment of leprosy and other dermatological diseases. The mechanism of action of dapsone is the inhibition of protein biosynthesis by competitive antagonism with para-aminobenzoic acid. The objectives of this research have been standardizedformulations for capsules of dapsone 50 and 100 mg using factorial design of mixtures, validation of an analytical method for quantification of the drug and its release from the pharmaceutical form capsule in addition to performing polymorphism study in crystalline forms. The validation has been performed by spectrophotometry in the UV region using fast, easy and low cost method, besides involving solvents less aggressive to the environment. This method presented linearity, precision, accuracy, robustness, limit of quantification and detection in compliance with the new requirements established by RDC 166/2017. The formulations proposed from the factorial design have been analyzed for mean weight, disintegration, dosage and uniformity of unit doses, and have been selected from statistical analysis for the study of drug release. The dissolution profile showed that for dapsone 100 mg the formulations F4, F10 and F14, presented dissolved dapsone content greater than 85% in 30 minutes, characterizing immediate release formulations. The comparison of the profiles obtained by the calculation of the dissolution efficiency (DE) showed that the three formulations selected presented Q30% above 85% in 30 minutes (F4 Q30% = 93.98, F10 Q30% = 85.96, F14 Q30% = 86.20), as well as satisfactory results for unit dose content and uniformity, and may be suggested as standard formulations for dapsone 100 mg in capsule pharmaceutical form. Formulations F1, F9, F15, selected for dapsone 50 mg, have been showed good results for drug content and uniformity of unit doses with an acceptance value (AV) of less than 15. The dapsone (active pharmaceutical ingredient) samples recrystallized using several solvents, showed diffraction pattern with predominance of form III that is the commercialized form. Analysis of variance showed that form III was statistically more soluble in hydrochloric acid, acetate buffer, phosphate buffer and water relative to the hydrate in the time required to reach equilibrium.