DEVELOPMENT AND EVALUATION OF LIPOSOMAL SELEXIPAG: A NOVEL ORAL DELIVERY SYSTEM FOR PULMONARY ARTERIAL HYPERTENSION

Abstract

Objectives: Pulmonary arterial hypertension (PAH) is a progressive and life-threatening condition characterized by increased pulmonary arterial pressure and vascular resistance. Selexipag, an oral prostacyclin receptor agonist, is effective in symptom management but suffers from poor aqueous solubility and limited bioavailability. This study aimed to develop and optimize a liposomal formulation of Selexipag-loaded liposomes (SLL) to enhance its oral bioavailability and therapeutic efficacy.

Methods: SLL were prepared using the thin film hydration method and optimized through Box–Behnken design with three independent variables: cholesterol, soya lecithin, and sonication time. The dependent variables included particle size (PS), entrapment efficiency (%EE), and zeta potential (ZP). Analysis of variance was used to analyze the experimental design, and the optimized formulation was characterized for compatibility, morphology, and release behavior.

Results: The optimized formulation exhibited a PS of 140.80±1.28 nm, %EE of 85.0±2.5%, and ZP of −25 mV, confirming good colloidal stability. In vitro drug release studies demonstrated a sustained release profile, achieving 75% drug release over 12 h compared to 40% from pure drug solution. Ex vivo permeation studies revealed a 1.8-fold increase in drug permeability through goat intestinal tissue for the liposomal formulation over the pure drug.

Conclusion: The developed Selexipag liposomal formulation significantly improved drug solubility, stability, and oral bioavailability potential, making it a promising delivery strategy for PAH management. The statistically validated optimization process confirmed the reliability of the formulation, laying a foundation for further clinical evaluation.