Abstract
Purpose of the present investigation was to explore the potential of butter oil (BO) as a novel permeation enhancer to enhance the drug concentration in the brain when given intranasally. Quetiapine fumarate (QF) was selected as a model drug since it undergoes extensive first-pass metabolism leading to poor oral bioavailability of 9%. QF:BO binary mixture was prepared by simple physical mixing in the ratio of 1:9 to 9:1. Diffusion study was performed to obtain optimized QF:BO ratio. QF loaded microemulsion (ME) system (QF ME) was developed by water titration method. The optimized ratio of QF:BO showing higher permeation for QF was added into ME to obtain QF:BO ME. Globule size of QF ME and QF:BO ME was found be 61.59 ± 0.54 and 133.30 ± 1.74 nm, respectively. Nasal diffusion data revealed that QF:BO ME showed higher permeation (85.45 ± 2.14%) for QF in comparison to QF ME (52.07 ± 2.07%) and QF solution (40.00 ± 2.01%). Nearly 4.6 folds higher brain bioavailability of QF:BO ME (384.11 ± 49.10%) compared to QF Solution (83.15 ± 9.82%) suggested higher transport of QF from QF:BO ME to rat brain. Overall, it was concluded that BO enhances the brain bioavailability of poorly permeable drugs across the olfactory neuroepithelium, thereby proving its potential in the area of brain drug delivery system.
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