Mathematical modelling of the transport of hydroxypropyl-beta-cyclodextrin inclusion complexes of ranitidine hydrochloride and furosemide loaded chitosan nanoparticles across a Caco-2 cell monolayer

作者：Sadighi Armin; Ostad S N; Rezayat S M; Foroutan M; Faramarzi M A; Dorkoosh F A^*

来源：International Journal of Pharmaceutics, 2012, 422(1-2): 479-488.

DOI：10.1016/j.ijpharm.2011.11.016

• Chitosan nanoparticles
• Furosemide
• Ranitidine hydrochloride
• Hydroxypropyl-beta-cyclodextrin
• Caco-2 cell
• Mathematical model

Chitosan nanoparticles (CS-NPs) have been used to enhance the permeability of furosemide and ranitidine hydrochloride (ranitidine HCl) which were selected as candidates for two different biopharmaceutical drug classes having low permeability across Caco-2 cell monolayers. Drugs loaded CS-NPs were prepared by ionic gelation of CS and pentasodium tripolyphosphate (TPP) which added to the drugs inclusion complexes with hydroxypropyl-beta-cyclodextrin (HP-beta CD). The stability constants for furosemide/HP beta CD and ranitidine HCl/HP-beta CD were calculated as 335 M-1 and 410 M-1, whereas the association efficiencies (AE%) of the drugs/HP-beta CD inclusion complexes with CS-NPs were determined to be 23.0 and 19.5%, respectively. Zetasizer and scanning electron microscopy (SEM) were used to characterise drugs/HP-beta CD-NPs size and morphology. Transport of both nano and non-nano formulations of drugs/HP-beta CD complexes across a Caco-2 cell monolayer was assessed and fitted to mathematical models. Furosemide/HP-beta CD-NPs demonstrated transport kinetics best suited for the Higuchi model, whereas other drug formulations demonstrated power law transportation behaviour. Permeability experiments revealed that furosemide/HP-beta CD and ranitidine HCl/HP-beta CD nano formulations greatly induce the opening of tight junctions and enhance drug transition through Caco-2 monolayers.

• 出版日期2012-1-17