INTRANASAL COLLOIDAL DRUG DELIVERY SYSTEM FOR BRAIN TARGETING OF DRUGS

Abstract

prevents the effective concentration at the brain due to newlinepresence of biological barriers and extensive first pass metabolism (9% and 36% newlinerespectively) and thus resulting into frequent dosing. The aim of the investigation newlinewas to develop intranasal microemulsion and mucoadhesive microemulsion system newlineof the quetiapine and rivastigmine to overcome the limitation of poor concentration newlineand obstructive barriers at the target site for improved bioavailability. Optimized newlineformulations of quetiapine and rivastigmine were characterized for various newlinephysicochemical and diffusion parameters. It was found that chitosan based newlinemucoadhesive microemulsion showed improved nasal diffusion for both the drugs in newlinecomparison to microemulsion and drug solution as a result of enhanced paracellular newlinetransport across nasal mucosa. In vitro cell line study demonstrated that chitosan newlinebased microemulsion system induced reversible opening of tight junctions and hence newlineshowed higher diffusion for quetiapine via paracellular route. Spray pattern and newlineplume geometry data showed satisfactory results with plume length in the range of newline10-12 cm, thus confirming the delivery of formulation into posterior nasal segment newlineand hence enhanced delivery to brain via olfactory route. In vivo pharmacokinetic newlinestudy demonstrated superior nasal bioavailability for both the drugs with chitosan newlinebased mucoadhesive microemulsion against individual drug solution, thus revealing newlinethe potential of chitosan as permeability enhancer and/or tight junction modulator newlinefor preferential nose to brain transport bypassing blood brain barrier. Results of newlinegamma scintigraphy study and in vivo pharmacokinetic parameters showed newlinesatisfactory correlation between pharmacokinetic parameters for intranasally newlineadministered chitosan loaded microemulsion. Overall, the above findings show newlinepromising results in the area of developing newline