Preparation and evaluation of spray-dried hyaluronic acid microspheres for intranasal delivery of fexofenadine hydrochloride.
Hyaluronic acid (HA)-based microspheres containing PEG 6000 and/or sodium taurocholate (NaTC) were prepared by the spray-drying method for nasal delivery of fexofenadine hydrochloride (HCl). Their physicochemical properties including particle size and drug contents were determined, while their morphology examined by a scanning electron microscope (SEM). The effects of the solubilizer (PEG 6000) and the permeation enhancer (NaTC) on the in vitro release characteristics of fexofenadine x HCl were observed. Moreover, the in vitro permeation of fexofenadine x HCl was determined using the human nasal cell (HNE) monolayers cultured on Transwell inserts. After nasal administration, fexofenadine x HCl in rabbit plasma was determined by the LC-MS/MS system. Fexofenadine x HCl-loaded microspheres were of spherical shape with 20-30 microm mean diameter. The loading efficiency was about 95%. In vitro release of fexofenadine x HCl from the microspheres was significantly increased with the addition of PEG 6000. Although NaTC did not alter the in vitro release of drug from the microspheres, its addition further increased the in vitro permeation of fexofenadine x HCl across the HNE cell monolayers. Moreover, the bioavailability of fexofenadine x HCl after nasal administration of the microsphere formulation to rabbits was increased up to about 48% while that of the control solution was only about 3%. These results indicated that the HA microsphere formulation could further be developed into a clinically useful nasal delivery system of fexofenadine x HCl.
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea.
Yeamin
Y
Huh
Hyun-Jong
HJ
Cho
In-Soo
IS
Yoon
Min-Koo
MK
Choi
Jung Sun
JS
Kim
Euichaul
E
Oh
Suk-Jae
SJ
Chung
Chang-Koo
CK
Shim
Dae-Duk
DD
Kim
D000281:Administration, Intranasal; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002460:Cell Line; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D020545:Respiratory Mucosa / Q000166:cytology; D013499:Surface Properties; D013656:Taurocholic Acid / Q000737:chemistry / Q000494:pharmacology; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics
D018926:Anti-Allergic Agents; D004337:Drug Carriers; D011092:Polyethylene Glycols; D013656:Taurocholic Acid; D016593:Terfenadine; D006820:Hyaluronic Acid; C093230:fexofenadine