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. 2014 Apr;4(2):151-60.
doi: 10.1016/j.apsb.2014.02.002. Epub 2014 Apr 2.

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

Rudree Pathak  1 , Ranjeet Prasad Dash  2 , Manju Misra  1 , Manish Nivsarkar  2
Affiliations

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

Rudree Pathak et al. Acta Pharm Sin B. 2014 Apr.

Abstract

Intranasal drug administration is receiving increased attention as a delivery method for bypassing the blood-brain barrier and rapidly targeting therapeutics to the CNS. However, rapid mucociliary clearance in the nasal cavity is a major hurdle. The purpose of this study was to evaluate the effect of mucoadhesive polymers in enhancing the delivery of nimodipine microemulsion to the brain via the intranasal route. The optimized mucoadhesive microemulsion was characterized, and the in vitro drug release and in vivo nasal absorption of drug from the new formulation were 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 of 250 nm and zeta potential value of -15 mV. In vitro and ex vivo permeation studies showed an initial burst of drug release at 30 min and sustained release up to 6 h, attributable to the presence of free drug entrapped in the mucoadhesive layer. In vivo pharmacokinetic studies in rats showed that the use of the mucoadhesive microemulsion enhanced brain and plasma concentrations of nimodipine. These results suggest that incorporation of a mucoadhesive agent in a microemulsion intranasal delivery system can increase the retention time of the formulation and enhance brain delivery of drugs.

Keywords: Blood–brain barrier; Entrapment; Nasal mucosa; Permeation; Pharmacokinetics.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Solubility of nimodipine in different oils, surfactants and cosurfactants. Data are expressed as mean±SD (n=6).
Figure 2
Figure 2
Pseudoternary phase diagram with varying ratios of the investigated quaternary system water/Labrasol/Transcutol/capmul MCM with (a) Smix in the ratio of 1:1 (b) Smix in the ratio of 2:1 and (c) Smix in the ratio of 3:1. The shaded areas indicate the clear o/w microemulsion system.
Figure 3
Figure 3
Representation of the obtained data for average particle size of in situ gelling mucoadhesive microemulsion.
Figure 4
Figure 4
In vitro release profile of nimodipine from different formulations. Data are expressed as mean±SD (n=6).
Figure 5
Figure 5
Ex vivo permeation study of nimodipine from different formulations. Data are expressed as mean±SD (n=6).
Figure 6
Figure 6
Histological photomicrographs of eosin–hematoxylin-stained nasal mucosa (10× magnification). (A) Control mucosa without application of formulation; (B) nasal mucosa after application of nimodipine in situ gelling mucoadhesive microemulsion.
Figure 7
Figure 7
Concentrations of nimodipine in (a) brain, (b) nasal mucosa and (c) plasma after intranasal administration of different formulations in rats. Data are expressed as mean±SD (n=6).
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