Brain targeted rivastigmine mucoadhesive thermosensitive In situ gel: Optimization, in vitro evaluation, radiolabeling, in vivo pharmacokinetics and biodistribution

摘要

The 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.