title: Microneedle-mediated delivery of donepezil: Potential for improved treatment options in Alzheimer's disease.
abstract: Transdermal drug delivery is an attractive route of drug administration; however, there are relatively few marketed transdermal products. To increase delivery across the skin, strategies to enhance skin permeability are widely investigated, with microneedles demonstrating particular promise. Hydrogel-forming microneedles are inserted into the skin, and following dissolution of a drug loaded reservoir and movement of the drug through the created channels, the microneedle array is removed intact, and can then be readily and safely discarded. This study presents the formulation and evaluation of an integrated microneedle patch containing the Alzheimer's drug, donepezil hydrochloride. The integrated patch consisted of hydrogel-forming microneedles in combination with a donepezil hydrochloride containing film. Formulation and characterisation of plasticised films, prepared from poly(vinylpyrrolidone) or poly (methyl vinyl ether co-maleic anhydride/acid) (Gantrez®) polymers, is presented. Furthermore, in vitro permeation of donepezil hydrochloride across neonatal porcine skin from the patches was investigated, with 854.71μg±122.71μg donepezil hydrochloride delivered after 24h, using the optimum patch formulation. Following administration of the patch to an animal model, plasma concentrations of 51.8±17.6ng/mL were obtained, demonstrating the success of this delivery platform for donepezil hydrochloride.
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Mary-Carmel
authors.initials: MC
authors.lastname: Kearney
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Ester
authors.initials: E
authors.lastname: Caffarel-Salvador
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Fallows
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Helen O
authors.initials: HO
authors.lastname: McCarthy
authors.affiliation: School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK. Electronic address: r.donnelly@qub.ac.uk.
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D019540:Area Under Curve; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D000077265:Donepezil; D007189:Indans / Q000008:administration & dosage*; D008297:Male; D008845:Microinjections; D009339:Needles; D010880:Piperidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Donepezil hydrochloride; Films; Microneedles; Patch; Transdermal drug delivery