Objectives: The main objective of this novel study was to develop midazolam hydrochloride
fast dissolving oral films (FDFs) using solvent casting method and to evaluate the characteristics of the
optimum formulation through in vitro and in vivo analysis. The FDFs are new favorable solid dosage
forms that deliver drugs rapidly to the blood circulation system and have great advantages in the emergent
control of severe neuropathic attacks in children.
Methods: Midazolam nanosuspensions were prepared using the ultrasonic method and then incorporated
in the hydroxypropyl methyl cellulose (HPMC)/pullulan polymeric matrix with other excipients
like glycerol and cellulose nanofiber as a softener and a compatibilizer, respectively. The prepared films
were evaluated for mechanical properties, morphology study, disintegration time, and dissolution time.
Results: SEM images of FDFs showed the uniform distribution of spherical nanoparticles in the polymeric
matrix. A film with 36% HPMC, 64% pullulan, and 21% glycerin was selected as the optimum
formulation by the Design Expert 7 software. The optimum film was stable for three months.
Conclusion: The pharmacokinetic parameters of midazolam oral film in comparison to coarse midazolam
suspension exhibited significant increase in AUC, Cmax, and a good decrease in Tmax. The overall
results showed the enhanced in vivo orotransmucosal absorption of poorly water-soluble drugs via the
insertion of drugs nanosuspension in buccal films.