HP-β-Cyclodextrin-Assisted Chitosan–STPP Nanoparticles for Enhanced Oral Delivery of Simvastatin: Formulation, Optimization and In-Vitro Evaluation

Poor aqueous solubility limits the oral bioavailability of simvastatin and reduces its therapeutic consistency. This study aimed to improve simvastatin dissolution and in-vitro performance by combining hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexation with chitosan–sodium tripolyphosphate (STPP) ionic-gelation nanoparticles and delivering the system in hard gelatin capsules. HP-β-CD complexes were prepared by solvent evaporation and characterised by phase-solubility and DSC analyses, which confirmed 1:1 complex formation and partial reduction of drug crystallinity. Simvastatin–HP-β-CD complexes were encapsulated in chitosan–STPP nanoparticles via ionic gelation. A central composite design (Design-Expert®) optimized chitosan and STPP levels for particle size, entrapment efficiency and drug release, yielding an optimized batch (S11: simvastatin 10 mg; chitosan 21 mg; STPP 9.46 mg; HP-β-CD 40 mg). The optimized nanoparticles exhibited narrow size distribution (80% drug within 30 minutes and achieved complete release by 45 minutes; similarity factor analysis versus the marketed Simvotin® 10 mg tablet produced f₂ = 79.45, indicating close profile equivalence. Short-term accelerated stability at 40 °C/75% RH for 30 days showed no significant degradation. The integrated HP-β-CD–chitosan nanoparticle approach effectively enhanced simvastatin dissolution and represents a promising platform for improving oral delivery of poorly soluble drugs.