Role of mucoadhesive polymers in enhancing delivery of nimodipine microemulsion to brain via intranasal route

Intranasal drug administration is receiving increasedattention as a delivery method for bypassing the blood–brain barrier and rapidlytargeting therapeutics to the CNS. However, rapid mucociliary clearance in the nasalcavity is a major hurdle. The purpose of this study was to evaluate the effect ofmucoadhesive polymers in enhancing the delivery of nimodipine microemulsion to thebrain via the intranasal route. The optimized mucoadhesivemicroemulsion was characterized, and the in vitro drug releaseand in vivo nasal absorption of drug from the new formulationwere evaluated in rats. The optimized formulation consisted of Capmul MCM as oil,Labrasol as surfactant, and Transcutol P as co-surfactant, with a particle size of250 nm and zeta potential value of −15 mV.In vitro and ex vivo permeationstudies showed an initial burst of drug release at 30 min andsustained release up to 6 h, attributable to the presence of freedrug entrapped in the mucoadhesive layer. In vivopharmacokinetic studies in rats showed that the use of the mucoadhesive microemulsionenhanced brain and plasma concentrations of nimodipine. These results suggest thatincorporation of a mucoadhesive agent in a microemulsion intranasal delivery systemcan increase the retention time of the formulation and enhance brain delivery ofdrugs.KEY WORDS: Blood–brain barrier, Entrapment, Permeation, Pharmacokinetics, Nasal mucosa