Enhanced Solubility and Dissolution of Selexipag via β-Cyclodextrin Inclusion Complexes: Formulation and Evaluation
Year: 2025
Type: article
Abstract: Introduction: Selexipag, a selective prostacyclin receptor (IP) agonist used in pulmonary arterial hypertension, suffers from poor aqueous solubility, limiting its oral bioavailability. Cyclodextrin complexation is a widely accepted technique to improve solubility and dissolution properties of hydrophobic drugs. This study aimed to enhance the solubility and dissolution rate of Selexipag by forming inclusion complexes with β-cyclodextrin. Methods: Inclusion complexes of Selexipag were prepared using three techniques: physical mixing, kneading, and solvent evaporation, each in 1:1 and 1:2 molar ratios with β-cyclodextrin. Phase solubility studies were performed to determine the stability constant. The prepared complexes were evaluated for drug content and in vitro dissolution using UV spectrophotometry and paddle method, USP Type II apparatus in 0.1 N HCl. Results: The phase solubility diagram exhibited an AL-type profile with a 1:1 stoichiometry and a stability constant of 164.56 M–¹. All formulations demonstrated acceptable drug content (98.3–102.2 %). Among the tested complexes, the kneading method at a 1:2 ratio (SK2) showed the highest drug release, achieving 94.2 % dissolution in 60 minutes, compared to 29.63 % for pure Selexipag. This enhancement is attributed to increased wettability, amorphization, and reduced crystallinity of the drug. Conclusion: Inclusion complexation of Selexipag with β-cyclodextrin markedly improved its solubility and dissolution rate. The kneading method with a 1:2 molar ratio proved most effective, offering a promising strategy for improving the oral delivery of poorly soluble drugs.
Source: Ars Pharmaceutica (Internet)
Institution: Mohan Babu University
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7116779818