Formulation and Optimization of Cilnidipine Nanoparticle-loaded Mucoadhesive Buccal Tablets using Quality by Design Approach for Enhanced Systemic Bioavailability
Mahallingan K, Vedamurthy JoshiIntroduction:
Cilnidipine, a calcium channel blocker used to treat hypertension, has poor oral bioavailability owing to extensive first-pass intestinal and hepatic metabolism. Buccal delivery offers an alternative route that bypasses hepatic first-pass metabolism and provides controlled systemic absorption. This study aimed to formulate and optimize a cilnidipine nanoparticle-loaded mucoadhesive buccal tablet using a Quality by Design (QbD) approach.
Methods:
Cilnidipine polymeric nanoparticles (polyvinylpyrrolidone K-30 with Pluronic F68), prepared by a solvent-evaporation method and characterized in our earlier work, were incorporated into a mucoadhesive matrix of hydroxypropyl methylcellulose (HPMC K4M and HPMC K15M) and Carbopol 934. Tablet hardness and cumulative drug release at 12 h were selected as the critical quality attributes and optimized using an Extreme Vertices Mixture Design (EVMD). Pre- and post-compression parameters, mucoadhesive strength, in vitro dissolution, swelling, release kinetics, and stability under ICH conditions were evaluated.
Results:
All formulations showed acceptable weight uniformity, hardness, and friability. The optimized formulation (BTF9) achieved 92.2% cumulative drug release over 12 h. The release data best fitted the Higuchi model (R² = 0.994), and the Korsmeyer-Peppas exponent indicated Fickian diffusion. Accelerated stability testing showed no significant change in the key parameters over six months.
Discussion:
Drug release and mucoadhesion were strongly influenced by polymer composition; the optimized polymer combination prevented burst release and sustained drug release while maintaining adequate mucoadhesion.
Conclusion:
The nanoparticle-loaded mucoadhesive buccal tablet is a promising candidate for improving the bioavailability of cilnidipine in the management of hypertension. This non-invasive, patient-friendly platform may reduce dosing frequency and improve adherence, and it provides a translational basis for future in vivo and clinical evaluation.