Pharmaceutical Research Of Donepezil Transdermal Patch

Donepezil (DPB) is a piperidine-based reversible acetylcholinesterase inhibitor. Currently DPB is the most prescribed pharmacological agent for the treatment of mild to moderate Alzheimer’s disease. It also plays the important role in improving the patient’s mental state and keeping the brain active. Now the drug dosage form of DPB has tablets and capsules. Researches have showed that alzheimer’s disease is the most common cause of dementia in elderly people and it needs long time to treatment. But for elderly alzheimer’s patients, it is often difficulty in swallowing, so administrating orally may lead to poor compliance of the patients. In addition, the large fluctuation of plasma concentration can lead the incidences of adverse events, so a transdermal drug delivery system can be considered as an alternative dosage form for donepezil. Transdermal drug delivery system can ensure essentially constant drug input, reduce or eliminate the liver first pass effect, reduce the side effect and improve compliance of the patients. It is a ideal mode of drug delivery.The aim of the present study was to develop and evaluate a novel drug-in-adhesive transdermal patch system for DPB by optimizing the drug-loading matrix and skin permeation enhancers. In this research, in vitro skin permeation tests, drug content and crystallization tests and stability tests were investigated to select suitable acrylic pressure-sensitive adhesive matrix. This paper determined the penetration parameters of DPB in vitro. The results showed that the partition coefficient between stratum corneum and viable skin is7.21, which showed that DPB is a compound with strong lipophilicity. Thus not only stratum corneum, but also viable skin acted as a barrier to the penetration of DPB. Penetration enhancers were used to promote transdermal permeability of donepezil in vitro. Different kinds of penetration enhancers and different concentration of penetration enhancers were investigated in vitro and the enhancement mechanism was explained. in vivo pharmacokinetics of the final formulation were studiedThe results indicated that a combination of Duro-Tak B and Duro-Tak C at a ratio of3:1volume per volume is suitable, which made it possible for donepezil to be contained in an adhesive layer at a concentration of as much as15wt%without donepezil crystal. But using this mixed pressure sensitive adhesive, donepezil has a low skin permeation rate and penetration enhancer are needed to improve the permeability of drugs. Compared to control group, the24h cumulative amount permeated of donepezil can be increased by2.7times using mixed enhances of aliphatic ester and organic acid. For in vivo studies two DPB patch systems were administered transdermally to rats while oral administration of DPB solution to rats was used as a control. The PK parameters, such as the time to reach the peak blood concentration (MRT)(Tmax), the maximum blood concentration (Cmax), mean residence time (MRT) and area under the curve (AUC0-t) were significantly different of transdermal administration compared with oral administration. In contrast to oral delivery, a sustained activity was observed over a period of48h after transdermal administration.