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Published on: November 14, 2018
Development of cannabidiol nanoemulsion for direct nose to brain delivery: statistical optimization,in vitroandin
Bakr Ahmed1, Md Rizwanullah1, Showkat Rasool Mir2
1Formulation Research Laboratory, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Abstract:
Cannabidiol (CBD) is a prescribed drug for epilepsy but has low oral bioavailability and gastric instability. Because of the direct link between the nasal cavity and the central nervous system, intranasal administration of CBD as nanoemulsions which are the small sized lipid carriers seem to improve the bioavailability. CBD-nanoemulsions (NEs) were made using Capryol 90, Tween 80, and Transcutol P as oil, surfactant, and co-surfactant, respectively, following aqueous titration approach. Then, using the Box-Behnken design, CBD-NE was statistically optimised for the selection of desirable excipient concentrations in order to create the optimal CBD-NE formulation. As independent variables in the statistical design, Capryol 90 (oil; coded asA), Tween 80 (surfactant; coded asB), and Transcutol P (co-surfactant; coded asC) were used. The dependent variables were droplet size (DS; coded asR1) and polydispersity index (PDI; coded asR2). The average DS, PDI, and the zeta potential of the optimized CBD-NEs were observed to be 88.73 ± 2.67 nm, 0.311 ± 0.015, and -2.71 ± 0.52 mV respectively. Pure CBD and lyophilized CBD-NEFourier-transform infraredspectra demonstrated no physicochemical interaction between excipients and the drug. Furthermore, differential scanning calorimetry and x-ray diffraction measurements revealed the amorphous CBD in the NE. As compared to pure CBD, the optimised CBD-NE showed considerably betterin vitrodrug release as well asex vivonasal permeability. The drug targeting efficiency and direct transport percentage of the optimised CBD-NEs were found to be 419.64% and 76.17%, respectively, in this research. Additionally, pharmacokinetic investigations after intranasal administration of CBD-NE revealed considerably higher drug concentrations in the brain with better brain targeting efficiency. As a result, the development of CBD-NE may be an excellent alternative for better intranasal delivery.
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