PELLETS DE ÁCIDO TARTÁRICO COMO NÚCLEO MODULADOR DE PH PARA FORMULAÇÕES DE CITRATO DE SILDENAFILA

Abstract

Pulmonary arterial hypertension (PAH) is a severe condition characterized by increased pressure in the pulmonary arteries, potentially leading to right heart failure. Sildenafil citrate (SC) is a phosphodiesterase type 5 (PDE5) inhibitor widely used in PAH treatment, but its low solubility and bioavailability limit its clinical efficacy. Therefore, this study aimed to develop a multiparticulate controlled-release formulation of SC, using tartaric acid pellets as the core, solid dispersion, and factorial design to optimize its dissolution and absorption. The methodology involved preparing SC solid dispersions using the Soluplus ® polymer and Tween ® 80 surfactant, followed by incorporating these dispersions into tartaric acid pellets coated with controlled-release polymers. An experimental design (DOE) was applied to assess the influence of variables on drug dissolution. The formulations were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRD), particle size distribution (PSD), scanning electron microscopy (SEM), and in vitro dissolution analysis with quantification by high-performance liquid chromatography (HPLC). The results demonstrated that solid dispersion significantly improved SC dissolution, and the coated pellets exhibited an adequate controlled-release profile, maintaining drug stability in biological media. Dissolution studies in FaSSIF buffer (pH 6.5) confirmed a gradual SC release, enhancing its absorption in the gastrointestinal tract and improving therapeutic efficacy. Thus, the use of tartaric acid pellets and solid dispersions proved to be a promising strategy to enhance SC’s oral bioavailability and optimize its clinical performance in PAH treatment. This innovative approach may contribute to the development of more effective pharmaceutical formulations, reducing the need for frequent dosing and improving patient adherence to treatment.