Cubosomes for Enhancing Intestinal Absorption of Fexofenadine Hydrochloride: In situ and in vivo Investigation

Abstract

Purpose The aim of this work was to probe cubosomes for enhanced intestinal absorption and oral bioavailability of poorly absorbable fexofenadine HCl (FEX-HCl). Materials and Methods Two cubosomal systems were fabricated utilizing glyceryl mono-oleate, a lyotropic mono lamellar lipid as oil phase and poloxamer407 as stabilizer at weight ratios of 8:2 and 7:3. The morphology of cubosomes was researched using transmission electron microscopy (TEM) and particle size was measured using photon correlation spectroscopy. FEX-HCl release was monitored in vitro. The effect of cubosomal encapsulation on intestinal absorption was assessed using in situ rabbit intestinal perfusion technique. Carrageenan induced rat paw edema model was utilized to monitor in vivo anti-inflammatory effect before and after cubosomal encapsulation. Results TEM revealed the existence of spherical and polygonal nanostructures arranged in honeycomb organization. Size measurement reflected nanoparticles with reduced size at higher poloxamer concentration. Release studies revealed liberation of FEX-HCl from cubosomes based on Higuchi kinetics model. The intestinal permeability data indicated incomplete absorption of FEX-HCl from simple aqueous solution with P-glycoprotein efflux contributing to this poor intestinal absorption. Incorporation of FEX-HCl in cubosomes enhanced membrane transport parameters. The intestinal absorption did not correlate with drug release suggesting that drug release is not the rate limiting with possible intact cubosomal transport. Cubosomal encapsulation of FEX-HCl significantly enhanced its in vivo anti-inflammatory efficacy compared to the aqueous FEX-HCl dispersion. Conclusion Cubosomes are promising novel carriers for enhancing intestinal absorption of FEX-HCl. Intact FEX-HCl-cubosomal absorption is possible via trans-lymphatic pathway but this requires further investigations.

Intestinal absorption pathways of lisinopril: Mechanistic investigations

“…All the prepared solutions were kept at 37 ± 0.5 ◦ C prior to intestinal in situ perfusion to simulate the body physiological temperature, with the solution pH values being adjusted to that of the perfused intestinal segment. The pH values of the prepared solutions were 6.6 for duodenum perfusion, 7.4 for jejuno‐ileum, and 6.8 for colon segment perfusion (Sultan et al., 2022).…”

Nanotechnology-based Therapeutic Strategies for Dry Eye Disease

“…Notably, drug absorption is generally facilitated through the transcellular pathway. 105 An in vivo study investigating the anti-inflammatory effects of fexofenadine hydrochloride in rabbits substantiated the superiority of a cubosomal carrier over an aqueous drug dispersion. 105 Huang et al reported the successful implementation of a cubosome-based drug delivery system for glaucoma treatment using timolol maleate (TM).…”

“…105 An in vivo study investigating the anti-inflammatory effects of fexofenadine hydrochloride in rabbits substantiated the superiority of a cubosomal carrier over an aqueous drug dispersion. 105 Huang et al reported the successful implementation of a cubosome-based drug delivery system for glaucoma treatment using timolol maleate (TM). Ex vivo corneal permeability experiments revealed an elevated penetration of TM cubosomes compared to commercially available eye drops, indicating an enhancement in corneal permeability, increased retention time, and improved bioavailability of ocular drugs for ocular disease treatment.…”

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“…Usually, drugs transported to lymph should be highly lipophilic and should be associated with chylomicron. M cell pathway and other mechanisms of lymphatic transport can co-occur in the cases that hydrophilic drug-loaded LLCs cannot be taken up into epithelial cells as intact particles [ 17 , 19 , 75 ]. Multiple mechanisms of lymphatic transport including M cells, chylomicrons, and transcellular and paracellular pathways at the tight junction of epithelial cells have been reported [ 65 , 67 , 76 ].…”