Orally disintegrating films based on pullulan and HPMC with carbopol-coated mucoadhesive nanoparticles for...

Dual-pattern drug release systems are a new type of drug delivery system designed to achieve both immediate and sustained drug release. This study developed a dual-pattern system by combining orally disintegrating films (ODFs) with mucoadhesive nanoparticles (NPs). The NPs were made from silk fibroin (SF) coated with carbopol polymer (CP) and loaded with midazolam (MID) (MID-CP/SFNPs). MID was chosen for its rapid onset, high lipophilicity, and excellent bioavailability, making it ideal for buccal administration. The MID-CP/SFNPs had an average diameter of 260.3 nm, a negative zeta potential of -22 mV, and an 80.6 % encapsulation efficiency. When tested against rabbit buccal mucosa, the CP/SFNPs demonstrated excellent mucoadhesive properties. Using a casting process, the MID-CP/SFNPs were combined with polysaccharide films made from pullulan and hydroxypropyl methylcellulose (PUL/HPMC) containing MID. The final product, MID-CP/SFNPs@MID-ODFs, had a uniform thickness of 68.8 μm, a consistent drug content of 87.5 %, significant flexibility (219 times), and a suitable disintegration time of 16 s. This formulation showed a rapid initial drug release of 45.6 % within the first 30 min, followed by a sustained release, resulting in a total of 91 % of the drug being released over 20 h. Histological evaluations confirmed no adverse effects on the microscopic structure of the buccal mucosa. This innovative system, combining ODFs with mucoadhesive NPs, showed promising results, making it a viable candidate for biomedical applications.