Abouhussein D.M.N.Khattab A.Bayoumi N.A.Mahmoud A.F.Sakr T.M.Pharmaceutics DepartmentNational Organization for Drug Control and Research (NODCAR)GizaEgypt; Labeled Compounds DepartmentHot Labs CenterAtomic Energy AuthorityP.O. Box 13759CairoEgypt; Radioactive Isotopes and Generator DepartmentHot Labs CenterAtomic Energy AuthorityP.O. Box 13759CairoEgypt; Pharmaceutics Chemistry DepartmentFaculty of PharmacyOctober University of Modern Sciences and Arts (MSA)GizaEgypt2020-01-092020-01-09201817732247https://doi.org/10.1016/j.jddst.2017.09.021PubMed ID :https://t.ly/eppWEScopusMSA Google ScholarThe purpose of our investigation was to promote the bioavailability and the brain delivery of rivastigmine tartarate (RV) through optimization of mucoadhesive thermosensitive in situ gel via intranasal (IN) route. The mucoadhesive in situ gels were developed using pluronic F127 (PF127) as thermogelling agent and different mucoadhesive polymers. A full factorial design was implemented to study the influence of three factors; pluronic type at two levels (PF127, PF127/PF68), mucoadhesive polymer type at four levels (HPMC, Chitosan, Carbopol 934 and NaCMC) and mucoadhesive polymer concentration at two levels (0.5 and 1%w/v). The studied responses were sol-gel temperature, consistency, gel strength, adhesion work and T50% of drug release. In vivo pharmacokinetic and biodistribution studies of the selected formula were investigated using radiolabeling approach using normal albino mice. The optimal RV in situ gel (PF127 and 1% Carbopol 934) showed significant transnasal permeation (84%) which was reflected in better distribution to the brain (0.54 %ID/g), when compared to RV IN solution (0.16 %ID/g) and RV IV intravenous solution (0.15 %ID/g). In conclusion, the investigated results showed the potential use of mucoadhesive in situ gel as a promising system for brain targeting of RV via the transnasal delivery system. � 2017 Elsevier B.V.EnglishBrain targetingIntranasalPluronicRadiolabelingRivastigmineThermosensitive in situ gelcarbopol 934chitosangelling agentpoloxamerrivastigminealbino mouseanimal experimentarea under the curveArticledrug absorptiondrug bioavailabilitydrug brain leveldrug delivery systemdrug releasefactorial designflow kineticsgelationin vitro studyin vivo studyisotope labelingmaximum plasma concentrationmousemucoadhesionmucoadhesive thermosensitive in situ gelnonhumanpharmacokinetic parametersradiochemistrysynthesistime to maximum plasma concentrationArticlehttps://doi.org/10.1016/j.jddst.2017.09.021PubMed ID :