Nose-to-Brain delivery of donepezil hydrochloride following administration of an HPMC-Me-β-CD-PEG400 nasal film in mice

Nasal administration has been demonstrated as an effective alternative for drug delivery to central nervous system (CNS), especially for use in neurodegenerative diseases. Donepezil Hydrochloride (DH) is a widely used acetylcholinesterase inhibitor for the management of Alzheimer's disease, able to cross the blood brain barrier after oral administration. However, DH undergoes extensive first-pass metabolism, a fact that limits the amount of drug reaching the CNS. The purpose of the present study was the nose-to-brain delivery in vivo of DH, formulated in the recently developed HPMC-Me-β-CD-PEG400 based polymeric nasal film. In particular, a pharmacokinetic study was carried out in comparison with oral (per os) administration of DH solution. Sparse sampling non-compartmental analysis was applied of all in vivo data to determine the pharmacokinetic parameters. The pharmacokinetic profiles after intranasal and per os administration revealed the pre-eminence of the nasal film in DH delivery, either to the CNS or bloodstream resulting in Cmax values 5.7 and 3.9 times as higher, respectively at each site. The effectiveness of nasal film is also witnessed by AUC values, as well as Drug Targeting Efficiency Percentage and nose-to-brain Direct Transport Percentage, respectively found equal to 212% and 53%.