Innovative SMEDDS Design for Selexipag: Boosting Solubility and Dissolution Efficiency

Selexipag (SeLx), a selective prostacyclin receptor agonist for pulmonary arterial hypertension (PAH), suffers from poor aqueous solubility, leading to limited oral bioavailability and variable therapeutic response. To overcome this challenge, a self-microemulsifying drug delivery system (SMEDDS) was designed and optimized using a simplex centroid mixture design. Nine formulations were developed by varying composition of oil (Capryol 90, X1: 10–15%), surfactant (Cremophor EL, X2: 55–65%), and co-surfactant (Transcutol HP, X3: 25–30%), followed by systematic evaluation of critical quality attributes (CQAs)such as self-emulsification time (R1), drug release at 30 min (R2), and globule size (R3). The formulations exhibited rapid self-emulsification (21–33 s), high drug release (83.89–93.81% within 30 min), and nanoscale globules (16.63–143.5 nm). Overlay plot analysis identified an optimized composition (X1 = 13.3%, X2 = 58.3%, X3 = 28.3%) that demonstrated superior performance with rapid emulsification (23 s), enhanced drug release (91.32%), nanosized globules (38.56 nm), and stable zeta potential (−12.8 mV), confirming colloidal stability upon dilution. The optimized SeLx-SMEDDS markedly improved dissolution and stability, offering a promising strategy to enhance the solubility, absorption, and ultimately oral bioavailability of SeLx. Improved dissolution is expected to translate into enhanced bioavailability and ultimately improved therapeutic efficacy, making this formulation approach clinically meaningful.