Poloxamer/cyclodextrin/chitosan-based thermoreversible gel for intranasal delivery of fexofenadine hydrochloride.
To enhance permeation and solubility of an intranasal delivery system of fexofenadine hydrochloride (FXD HCl), a new formulation using poloxamer 407 (P407)/hydroxypropyl-β-cyclodextrin (HP-β-CD)-based thermoreversible gels with chitosan, was developed. Prepared gels were characterized by gelation temperature, viscosity, viscoelasticity, and drug release profile. The in vitro permeation study was performed in primary human nasal epithelial cell monolayers cultured by air-liquid interface method. The addition of chitosan caused the slight elevation of gelation temperature and viscosity-enhancing effect. Viscosity enhancement by the incorporation of chitosan caused the retardation of drug release from P407 gels in in vitro release test. The in vitro permeation profile showed that the increase in chitosan content (0.1% and 0.3%, w/v) significantly enhanced the permeation of FXD HCl. After intranasal administration of P407/HP-β-CD-based thermoreversible gels containing 0.1% and 0.3% of chitosan in rabbits at 0.5 mg/kg dose, plasma concentrations of FXD HCl were significantly higher than those of nasal solutions (p < 0.05). In particular, the bioavailability of the optimized thermoreversible gel containing 0.3% chitosan was about 18-fold higher than that of the solution type. These results suggested the feasibility that thermosensitive gels could be used as an effective dosage form to enhance the nasal absorption of FXD HCl.
Cho
Hyun-Jong
HJ
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Balakrishnan
Prabagar
P
Park
Eun-Kyoung
EK
Song
Ki-Won
KW
Hong
Soon-Sun
SS
Jang
Tae-Young
TY
Kim
Kyu-Sung
KS
Chung
Suk-Jae
SJ
Shim
Chang-Koo
CK
Kim
Dae-Duk
DD
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000281:Administration, Intranasal; D000818:Animals; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D005782:Gels / Q000737:chemistry; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D013696:Temperature; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014783:Viscosity; D047392:beta-Cyclodextrins / Q000737:chemistry*
D005782:Gels; D039563:Histamine H1 Antagonists, Non-Sedating; D047392:beta-Cyclodextrins; D020442:Poloxamer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D016593:Terfenadine; D048271:Chitosan; C093230:fexofenadine