Abstract
Donepezil is an acetylcholinesterase inhibitor and is the most commonly prescribed medication for treating Alzheimer's disease. However, the currently marketed donepezil products are once daily oral formulations with side effects such as nausea, vomiting and weight loss, etc. and the patient's compliance is also very low. Recently, once or twice weekly donepezil patch formulations have been developed but these formulations still have disadvantages such as skin irritation, effect of sweating, shower, etc. on in vivo donepezil release rate. One month release injectable of donepezil using biodegradable polymers can be a good alternative to increase patient compliance and reduce these side effects or disadvantages. In this study, GB-5001, once monthly donepezil depot injectable was prepared using InnoLAMP technology, which enables easy mass production of uniform biodegradable microspheres. Pharmacokinetic studies were performed after a single intramuscular injection of GB-5001 in male SD rats and Beagle dogs. Dose dependency and PK parameters were evaluated by analyzing plasma donepezil concentration by LC/MS/MS after administering three different doses of GB-5001 in each species. GB-5001, one-month release donepezil microspheres with uniform size, was successfully prepared by InnoLAMP technology. In rat PK study of GB-5001 after a single intramuscular injection, plasma donepezil concentration was kept within the therapeutic range for more than one month. Three different doses of GB-5001 showed Tmax of 14 days and dose dependent Cmax values. Moreover, the area under the curve of GB-5001 was also observed to be increased with accordance with the dose. Dog PK study after a single intramuscular injection of GB-5001 at three different doses also showed similar in vivo donepezil release profiles and dose dependent Cmax and AUC values as in rat experiments. Using proprietary InnoLAMP platform technology, we successfully produced uniform sustained release donepezil microspheres for Alzheimer's disease. Dose dependent and longer than one month releasing PK Results in rats and dogs of this formulation, GB-5001, indicate that GB-5001 could be used as an excellent alternative delivery Methods of donepezil for Alzheimer's disease treatment. Currently, scale-up and GMP manufacturing processes are under development to initiate human clinical trial of GB-5001.
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