Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

Surjyanarayan Mandal,Bharat Bhushan Subudhi,Krishna Chuttani,Snigdha Das Mandal

doi:10.1590/s1984-82502015000300024

Abstract

This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI) was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI) and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM) study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS). The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

Highlights

Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to be protective in animal models of Parkinson’s disease (PD) and regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of PD in humans (Lang, Lozano, 1998, Tansey, Goldberg, 2010)
Some other findings showed that NSAIDs may delay or prevent the onset of PD
Since Capmul MCM is a biocompatible vehicle and has got maximum drug solubilizing capacity compared to the screened oils i.e., 62.54 ± 1.23 mg/mL, it was selected as oil phase

Summary

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) appear to be protective in animal models of Parkinson’s disease (PD) and regular use of NSAIDs may reduce the risk of PD in humans (Lang, Lozano, 1998, Tansey, Goldberg, 2010). The clinical usefulness of ibuprofen is limited by its high first-pass metabolism in liver, which leads to low oral bioavailability and poor brain entry due to over expression of p-glycoprotein (Chen et al, 2008). Looking for alternative routes of administration to improve therapeutic effects is necessary. Drug delivery through nasal route has received a lot of attention, because it offers several advantages including rapid absorption of drug, avoidance of hepatic first-pass metabolism, and drug delivery preferentially to brain via the olfactory region (Woensel et al, 2013). The nasal route to the brain may provide a better alternative to oral administration of Ibuprofen. Effective nasal delivery volume in human is ≤400μl (200μl per nostril), normal solution did not provide satisfactory solubility for nasal delivery of Ibuprofen

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