Role of Omega-3 Fatty Acids and Butter Oil in Targeting Delivery of Donepezil Hydrochloride Microemulsion to Brain via the Intranasal Route: a Comparative Study.

Dignesh Khunt, Meenakshee Shrivas, Suryanarayana Polaka, Piyush Gondaliya, Manju Misra

AAPS PharmSciTech 2020 Jan 03

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In order to investigate the possible role of butter oil (BO) and omega-3 fatty acids-rich fish oil (O3FO) in the delivery of donepezil hydrochloride microemulsion (DH-ME) to the brain via intranasal route, the present study was conducted. DH:BO and DH:O3FO binary mixtures (9:1 to 1:9) were prepared by simple physical mixing and subjected to in vitro diffusion study. Ratios of DH:BO and DH:O3FO, which showed the highest diffusion, were selected for further development of microemulsion (ME). Globule sizes of DH-BO-ME and DH-O3FO-ME were found to be 87.66 ± 5.23 nm and 88.59 ± 8.23 nm, respectively. Nasal histopathological study and in vitro cytotoxicity study revealed the safety of the formulation. Higher percentage of nasal diffusion was found with DH-BO-ME (71.22 ± 1.21%) and DH-O3FO-ME (62.16 ± 1.23%) in comparison to DH-ME (59.69 ± 1.74%) and DH solution (55.01 ± 1.19%), which was further supported by in vitro cell permeability study. After intranasal administration, %bioavailability of drug in the rat brain (Sprague-Dawley rats)(on the basis of DH-ME IV) was higher with DH-BO-ME (313.59 ± 12.98%) and DH-O3FO-ME (361.73 ± 15.15%) in comparison to DH-ME (168.62 ± 6.60%) and DH solution (8.960 ± 0.23%). The results of ex vivo diffusion study and in vivo pharmacokinetic study suggested that BO and O3FO helped in enhancing the nasal permeability and the brain uptake of drug when administered intranasally.

Citation

Dignesh Khunt, Meenakshee Shrivas, Suryanarayana Polaka, Piyush Gondaliya, Manju Misra. Role of Omega-3 Fatty Acids and Butter Oil in Targeting Delivery of Donepezil Hydrochloride Microemulsion to Brain via the Intranasal Route: a Comparative Study. AAPS PharmSciTech. 2020 Jan 03;21(2):45