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

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.Uniterms: Ibuprofen/brain-targeting. Ibuprofen/intranasal administration. Ibuprofen/mucoadhesion. Mucoadhesive microemulsion gel. Drugs/design. Transmission electron microscopy.O objetivo deste trabalho foi planejar microemulsão/mucoaesiva em gel a fim de melhorar a captação cerebral de ibuprofeno por via intranasal. A microemulsão para mucoadesão com ibuprofeno (MMEI) foi desenvolvida pela incorporação de policarbofil como polímero mucoadesivo em microemulsão otimizada (MEI) com base em Capmul (MCM) e foi submetida à caracterização, estabilidade, mucoadesão e naso-ciliotoxicidade. A captação cerebral de ibuprofeno pela via nasal foi estudada por meio de estudo de biodistribuição em ratos albinos suíços. MEI se mostrou transparente, estável e não ciliotóxica, com 66,29 ± 4,15 nm, -20,9 ± 3,98 mV e 98,66 ± 1,01%, respectivamente, de tamanho médio dos glóbulos, potencial zeta e conteúdo do fármaco. O estudo revelou o estreita distribuição do tamanho dos glóbulos de MEI. Após administração intranasal única de MMEI e MEI, em dose de 2,86 mg/kg, a captação de ibuprofeno no bulbo olfativo foi em torno de 3,0 e 1,7 vezes maior, comparativamente, à injeção endovenosa de ibuprofeno (IDS). As taxas de ASC em tecido cerebral em relação ao plasma, obtidas após administração da MMEI nasal, foram, significativamente, mais elevadas do que aquelas observadas após a administração intravenosa de IDS. Os resultados do presente estudo mostraram que a microemulsão/mucoadesiva em gel poderia ser uma abordagem promissora para o direcionamento cerebral de ibuprofeno por via intranasal.Unitermos: Ibuprofeno/captação cerebral. Ibuprofeno/administração intranasal. Ibuprofeno/mucoadesão. Microemuls...

KLVFF Conjugated Curcumin Microemulsion-Based Hydrogel for Transnasal Route: Formulation Development, Optimization, Physicochemical Characterization, and Ex Vivo Evaluation

“…The pH value of KCME was assessed using a digital pH meter (pH meter, Metrohm, Herisau, Switzerland). For the pH of the KCMEG, 1.0 g of KCMEG was dispersed in 100 mL of distilled water, and then the pH was measured after storing it for 2 h [ 73 ]. The device was first standardized using pH 4 and 7 buffers.…”

Formulation, Optimization and Characterization of Ibuprofen Loaded Microemulsion System Using D-Optimal Mixture Design

“…With the t-test applicable to the difference between the estimated coefficients of the mixture, the value p<0.0001 for the oil coefficient shows that the variation of the transmission response is significantly sensitive to the variation of oil. As already discussed, the transmittance of microemulsion systems increased with decreasing oil content and increasing surfactant mixture due to the efficient emulsification of oil into smaller droplets [25,37,41].…”

“…The percent transmittance of microemulsions was determined using UV spectrophotometer (Shimadzu UV 2450; Japan) at a wavelength of 650 nm using distilled water as the reference [25].…”

Ultrasound‐Assisted Slug‐Flow Tubular Crystallization for Preparation of Fine Ibuprofen Crystals

“…It is generally believed that particles with a particle size of 5-10 μm are suitable for nasal delivery and some researchers have developed preparation methods of ibuprofen crystals for inhaled administration by adding excipients, wet milling or spray drying [29][30][31][32][33][34]. However, ibuprofen particles obtained by above methods are usually amorphous and their stability is not ideal.…”