Formulation Development of Functional Oil Loaded Rizatriptan Benzoate Microemulsion: An In Vitro and Ex Vivo Insight

Abstract

The present study investigated the formulation development of functional oils such as linseed oil, almond oil, and walnut oil and their comparative evaluation for permeation enhancement. Pre-formulation studies like solubility study and emulsification study were performed for selecting microemulsion components. The microemulsion region was obtained by generating pseudo ternary phase diagrams. The final formulations were selected by the OFAT model and characterized for appearance, globule size, polydispersity index, zeta potential, drug content, dilution potential, centrifugation stability, and pH. Furthermore, in vitro dissolution and ex vivo permeation studies were performed. All final formulations were found colourless, clear and transparent without phase separation or precipitation. All formulations showed mean globule size below 20 nm, polydispersity index less than 0.1, and exhibited zeta potential of -30 mV. All formulations showed drug content greater than 97 % and pH in the range of 5-6. The in vitro drug release study showed 89.12 %, 91.06 % and 101.21 % drug release by linseed oil, almond oil and walnut oil-loaded microemulsions respectively whereas pure drug solution exhibited 103.48 % drug release at the end of 6 h. The drug release from all three formulations was best fitted into the Higuchi model whereas plain drug fitted into the Hixson Crowell model. An ex vivo permeation study revealed that all formulations showed higher steady state flux than the drug solution with ~1.25 fold enhancement. The study concluded that the use of functional oils significantly improved permeation and drug release which can further improve bioavailability upon in vivo assessment in the suitable animal models. Key words: Microemulsion, polyunsaturated fatty acids, rizatriptan benzoate, functional microemulsion, flaxseed oil, almond oil, walnut oil, in vitro-ex vivo correlationThe burden of non-communicable and injuryrelated neurological diseases is increasing in India. Non-communicable neurological diseases (stroke, migraine, epilepsy, cerebral palsy, Alzheimer's disease, dementia, brain cancer, Parkinson's disease, multiple sclerosis, motor neuron diseases, and other neurological disorders, etc.) increased their contribution to total Disability-Adjusted Life Years (DALYs) in India from 4 % in 1990 to 8.2 % in 2019 and will continue to increase further. However, communicable neurological disorders (encephalitis, meningitis, and tetanus) dropped their contribution from 4.1 %-1.1 % in 2019. Injury-related neurological diseases accounted for 0.6 % of total DALYs in 2019, compared to 0.2 % in 1990. The fraction of total DALYs attributable to all neurological illnesses (comprising communicable, non-communicable and injuryrelated disorders) increased slightly from 8.3 % in 1990 to 9.9 % in 2019 in India [1] . Everyday risk factors such as stress, lack of physical activity, poor nutrition, obesity, high plasma cholesterol levels, smoking, drinking, or may have a role in the relatively high prevalence of neurodegenerative disord...