Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer's disease.
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 micromolding 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°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 microneedles was investigated using four administrations of a pharmacokinetic test: (1) two oral administration groups (283μg/kg and 692μg/kg) and (2) two microneedle administration groups (283μg/kg and 692μg/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 5min of insertion. As measured by Cmax 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.
Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University, Gyeonggi-do, Republic of Korea.
Ji-Yeon
JY
Kim
Department of Medicine, Chung-Ang University, Seoul, Republic of Korea.
Mee-Ree
MR
Han
Yuhan Research Institute, Yuhan Corporation, Gyeonggi-do, Republic of Korea.
Yong-Han
YH
Kim
Yuhan Research Institute, Yuhan Corporation, Gyeonggi-do, Republic of Korea.
Seung-Woo
SW
Shin
Yuhan Research Institute, Yuhan Corporation, Gyeonggi-do, Republic of Korea.
Su-Youn
SY
Nam
Department of BioNano Technology and Gachon BioNano Research Institute, Gachon University, Gyeonggi-do, Republic of Korea. Electronic address: pa90201@gachon.ac.kr.
Jung-Hwan
JH
Park
D000279:Administration, Cutaneous; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077265:Donepezil; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009339:Needles; D010880:Piperidines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012995:Solubility
D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
Donepezil hydrochloride; High content; Pharmacokinetic study; Tip-loaded microneedle