Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer's disease

Abstract

Donepezil hydrochloride (DPH) is often used in the treatment of Alzheimer's disease. A new treatment method was developed by encapsulating high DPH content in the tips of dissolving microneedles for rapid, transdermal delivery of a predetermined dose of DPH. The microneedles were prepared by a micro molding method using a hydroxy-propyl-methyl-cellulose (HPMC)-ethanol/water mixture (80:20, v/v) for the tips and carboxy-methyl cellulose (CMC)-water for the base of the needles. The micromolding method involved centrifuging a DPH-HPMC-ethanol/water mixture at 10 degrees C to obtain tips with sufficient mechanical strength. To test their mechanical strength, microneedles with different DPH content were inserted into porcine skin. Then the amount of DPH encapsulated in the microneedles was measured using high-performance liquid chromatography. The efficiency of administering DPH tip-loaded micro needles was investigated using four administrations of a pharmacokinetic test: (1) two oral administration groups (283 mu g/kg and 692 mu g/kg) and (2) two microneedle administration groups (283 mu g/kg and 692 mu g/kg). High DPH content (up to 78%, w/w) was encapsulated in the microneedle tips without serious loss of mechanical strength by using a mixture of hydroxy-propyl-methyl-cellulose (HPMC) and ethanol/water mixture (80:20, v/v). Because of the distribution of DPH in the tips, 95% of the DPH was delivered into porcine skin after 5 min of insertion. As measured by C-max and AUC, transdermal delivery of DPH tip loaded microneedles was more effective compared to oral administration of the same dose of DPH. Transdermal delivery could replace oral administration of DPH. (C) 2016 Elsevier B.V. All rights reserved.