Fast disintegrating dosage forms of mucoadhesive-based nanoparticles for oral insulin delivery: optimization to in vivo evaluation.

The aim of this work was to develop fast disintegrating dosage forms, including fast disintegrating tablets (FDTs) and films (FDFs), for oral insulin delivery incorporating mucoadhesive thiolated chitosan (TCS)-based nanoparticles (NPs). Cyclodextrin (CD)-insulin complexes were formed to prevent insulin from degradation and further optimally prepare NPs in order to improve the mucoadhesive properties. After that, these NPs were incorporated into the dosage forms and then evaluated for their morphology as well as physical and mechanical properties. The disintegration time, insulin content, mucoadhesive properties, insulin release, cytotoxicity, in vivo hypoglycemic effect, and stability of dosage forms were studied. Results showed that the CD-insulin complexes were successfully encapsulated into the mucoadhesive NPs. The 15 %w/w CD-insulin complex-loaded NPs, which were probably dispersed and/or fused into the dosage forms, showed promising characteristics, including rapid disintegration as well as good physical and mechanical properties to withstand erosion during handling and storage. The porous structure of the FDTs promoted liquid flow and induced rapid disintegration. The dosage forms provided buccal mucoadhesion before, during, and/or after the disintegration. The FDFs containing hydroxypropyl β-cyclodextrin (HPβCD)-insulin complex-loaded NPs increased mucoadhesion, increasing insulin release. Furthermore, these dosage forms provided excellent in vivo hypoglycemic response with a prolonged effect in diabetic mice and had no cytotoxicity toward the gingival fibroblast cells. In addition, they were stable at temperatures between 2 and 8 °C for three months. The results indicate that these formulations could be applied as promising dosage forms for use in oral insulin delivery.