Biodegradable donepezil lipospheres for depot injection: optimization and in-vivo evaluation

The purpose of this study was to develop an injectable depot liposphere delivery system with high loading capacity for controlled delivery of donepezil to decrease dosing frequency and increase patient compliance.

A 3(2) full factorial design was employed to study the effect of lipid type and drug-to-lipid ratio on the yield, encapsulation efficiency, mean diameter and the time required for 50% drug release (t(50%) ). The pharmacokinetic behaviour of the lipospheres in rabbits was studied using tandem mass spectrometry.

The yields of preparations were in the range of 66.22-90.90%, with high encapsulation efficiencies (89.68-97.55%) and mean particle size of 20.68-35.94 µm. Both lipid type and drug-to-lipid ratio significantly affected t(50%) (P<0.0001), where the lipids can be arranged: glyceryl tripalmitate>compritol>cetyl alcohol, and the drug-to-lipid ratios can be arranged: 1:40>1:20>1:10. The flow time of lipospheres through 19-gauge syringe needle was less than 6s indicating good syringeability. The mean residence time of the subcutaneous and intramuscular lipospheres was significantly higher than the solution (almost 20 fold increase), with values of 11.04, 11.34 and 0.53 days, respectively (P<0.01).

Subcutaneous and intramuscular delivery of donepezil glyceryl tripalmitate lipospheres achieves depot release, allowing less frequent dosing.