Tartaric acid pellets as a core for extended-release of sildenafil citrate: development via solid dispersion and factorial design.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by elevated pulmonary arterial pressure, causing vascular remodeling and eventual right heart failure. Sildenafil citrate (SC), a selective phosphodiesterase-5 inhibitor, used in PAH management; however, its clinical utility is limited by poor aqueous solubility and low oral bioavailability (38 - 42%).

Objective: This study aimed to develop an extended-release sildenafil citrate formulation using tartaric acid pellets as the core, with a solid dispersion system incorporating Soluplus® and Tween^® 80 to enhance solubility and sustain release.

Method: A spray-drying technique was employed to prepare the solid dispersion, and a factorial design was used to optimize the formulation parameters. The optimized dispersion was layered onto inert tartaric acid and subsequently coated with 7% ethylcellulose and hypromellose (80:20) to achieve sustained drug release.

Results: The optimized formulation (DS03), comprising a 1:1 ratio of Soluplus^®: to SC with 10% Tween^® 80, increased SC solubility by 50% in FaSSIF (pH 6.5), from 0.04 to 0.06 mg/mL. Incorporation into coated tartaric acid pellets further enhanced solubility to 0.51 mg/mL, representing a 1,175% improvement over pure SC (a 12.75-fold increase). The formulation provided sustained drug release for up to 12 hours, with a mean dissolution time (MDT) of 190 minutes, compared to less than 20 minutes for the immediate-release reference (Revatio^®).

Conclusion: This novel extended-release system significantly improves SC solubility and enables prolonged release, which may reduce dosing frequency and adverse effects, enhancing patient adherence. Further studies on stability and pharmacokinetics are warranted to support clinical application.