Chitosan nanoparticles enhance permeability of rizatriptan in mucoadhesive buccal films: A promising approach for improved drug delivery

The main causes of Rizatriptan's lower therapeutic efficacy in the treatment of migraines are its high first pass metabolism and low oral bioavailability. Rizatriptan-chitosan nanoparticles (RCNPs) are prepared by the ionic gelation process. Based on the highest value of % EE (94.28±1.26%) the RCNPs2 is selected as optimized ones and further characterized for particle size, ZP, FTIR spectroscopy and in vitro drug release. The optimized NPs poses the average particle size of 476.6nm, ZP of +22.6mv, FTIR reveals the no major link existed between the drug and excipients used in the study and they followed first order kinetics (r² = 0.9644) and non-Fickian super case II drug release mechanism (n=1.3412). The optimized NPs (RCNPs2) were incorporated into the thin mucoadhesive buccal films (BFs) by a conventional solvent casting method; utilizing an individual or combination of polymers (POLYOX and/or guar gum). Prepared BFs (RCNBFs1-6) were examined for mechanical, mucoadhesive, swelling and in vitro drug release characteristics. The RCNBFs6 with highest mucoadhesive strength (7.5±0.22 N) and the maximum amount of drug released at 6^th h (95.7±1.32) is considered as optimized one and further screened for FTIR spectroscopy, Scanning Electron Microscope (SEM) analysis and ex vivo permeation study with goat mucosa. The optimized BFs (RCNBFs6) followed first order kinetics (r²=0.9644) and non-Fickian super case II drug release mechanism (n=1.3412). It exhibited significantly higher (p<0.005) buccal flux (71.94±8.26μg/cm²/h) with a short lag time. The permeation is ~1.7-folds enhanced in optimized BFs with nanoparticles, when compared with the film with plain drug.