Formulation and In-vivo Pharmacokinetic Consideration of Intranasal Microemulsion and Mucoadhesive Microemulsion of Rivastigmine for Brain Targeting.
PURPOSE
Presence of tight junctions in blood brain barrier (BBB) pose a major hurdle for delivery of drug and severely affects adequate therapeutic concentration to reach the brain. In present work, we have selected Rivastigmine hydrogen tartrate (RHT), a reversible cholinesterase inhibitor, which exhibits extensive first-pass metabolism, resulting in limited absolute bioavailability (36%). RHT shows extremely low aqueous solubility and poor penetration, resulting in inadequate concentration reaching the brain, thus necessitating frequent oral dosing. To overcome these problems of RHT, microemulsion (ME) and mucoadhesive microemulsion (MME) of RHT were formulated for brain targeting via intranasal delivery route and compared on the basis of in vivo pharmacokinetics.


METHODS
ME and MME formulations containing RHT were developed by water titration method. Characterization of ME and MME was done for various physicochemical parameters, nasal spray pattern, and in vivo pharmacokinetics quantitatively and qualitatively (gamma scintigraphy studies).


RESULTS
The developed ME and MME were transparent having globule size approximately in the range of 53-55 nm. Pharmacokinetic studies showed higher values for Cmax and DTP for intranasal RHT: CH-ME over RHT-ME, thus indicating the effect of chitosan in modulating tight junctions, thereby enhanced paracellular transport of RHT.


CONCLUSION
Gamma scintigraphy and in vivo pharmacokinetic study suggested enhanced RHT concentration, upon intranasal administration of RHT:CH-ME, compare with other groups administered formulations intranasally. These findings suggested the potential of non-invasive intranasal route for brain delivery, especially for therapeutics, facing challenges in oral administration.
['Shah|Brijesh|B|', 'Khunt|Dignesh|D|', 'Misra|Manju|M|', 'Padh|Harish|H|http://orcid.org/0000-0003-2305-6229']
D000281:Administration, Intranasal D000327:Adsorption D000544:Alzheimer Disease D000818:Animals D001682:Biological Availability D001692:Biological Transport D001812:Blood-Brain Barrier D001921:Brain D048271:Chitosan D002800:Cholinesterase Inhibitors D002802:Cholinesterases D002851:Chromatography, High Pressure Liquid D004339:Drug Compounding D016503:Drug Delivery Systems D065546:Drug Liberation D004655:Emulsions D006801:Humans D007553:Isotope Labeling D009297:Nasal Mucosa D051381:Rats D017207:Rats, Sprague-Dawley D000068836:Rivastigmine D012995:Solubility D014018:Tissue Distribution
microemulsion rivastigmine brain targeting intranasal route alzheimer’s disease