Development of Azilsartan Nanoparticles via Hydrolysis for Enhanced Drug Delivery

Background

Hypertension is a major global health concern and a primary risk factor for cardiovascular morbidity and mortality. Azilsartan medoxomil, a novel angiotensin II receptor blocker, is effective in blood pressure reduction but suffers from poor aqueous solubility and variable oral bioavailability. Nanoparticle-based delivery systems, particularly using chitosan, offer a strategy to overcome these limitations by enhancing solubility, dissolution, and stability.

Materials and Methods

Azilsartan medoxomil nanoparticles (AZL-NP) were prepared using the ionic gelation technique with chitosan and sodium tripolyphosphate as cross-linkers. Preformulation studies included solubility testing, FTIR compatibility, and melting point determination. Nanoparticles were characterized for particle size, Polydispersity Index (PDI), zeta potential, and drug content. Morphological evaluation was conducted using Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM), while X-ray Diffraction (XRD) was performed for structural analysis. Lyophilized nanoparticles were compressed into tablets and subjected to physicochemical and in vitro release studies.

Results and Discussion

Optimized formulation showed a mean particle size of 479.4 nm, PDI of 0.239, and zeta potential of +34.2 Mv, confirming good stability. AFM and SEM revealed nanoparticles with irregular to semi-spherical morphology, and XRD indicated partial crystallinity. Formulated tablets complied with pharmacopeia limits for hardness, friability, and disintegration. In vitro dissolution studies demonstrated rapid and enhanced release, with 95.85% of drug released within 60 min, compared to conventional tablets. Release kinetics followed first-order and korsmeyer-peppas models, indicating non-fickian diffusion.

Conclusion

Azilsartan medoxomil loaded chitosan nanoparticles were successfully developed and optimized, showing improved solubility, dissolution rate, and drug release compared to conventional formulations. The nanoparticle-based system demonstrates significant potential to enhance the oral bioavailability and therapeutic efficacy of Azilsartan in hypertension management.