Formulation and evaluation of ondansetron nasal delivery systems.
This study aimed to formulate and evaluate nasal delivery systems containing ondansetron hydrochloride. In the in vitro study, the permeation rate with the addition of 10% polyethylene glycol 300 (PEG 300) to aqueous solution containing 0.01% benzalkonium chloride (BC) and 10% sulfobutylether beta-cyclodextrin sodium salt (SBCD) was somewhat more rapid up to 1.5h compared to the addition of 10% PG. The permeation flux increased as the drug concentration increased regardless of the vehicles used. The addition of nicotinamide or chitosan to aqueous drug solution (40 mg/ml) with 10% PEG 300 and 0.01% BC rather decreased permeation rate and delayed lag time. Even though cyclodextrins including SBCD or dimethyl-ss-cyclodextrin failed to show permeation enhancing effects of ondansetron hydrochloride, the addition of 10% SBCD to aqueous solution containing 10% PEG 300 and 0.01% BC could be a good candidate for ondansetron nasal delivery systems because of its safety profile, stable storage in refrigerator and solubilizing effect. With the above formulation, the nasal delivery system increased AUC0-2h and Cmax by 2.1 and 1.7 times compared to those of oral delivery, respectively while there was no difference found in AUC0-2h with intravenous administration. Therefore, the nasal delivery system of ondansetron hydrochloride formulated in this study was feasible for nasal administration.
Cho
Eunsook
E
College of Pharmacy, Dongduk Women's University, Seoul 136-714, South Korea.
Gwak
Hyesun
H
Chun
Inkoo
I
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D005079:Excipients; D006207:Half-Life; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D009297:Nasal Mucosa; D017294:Ondansetron / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability; D014677:Pharmaceutical Vehicles; D011817:Rabbits; D051381:Rats; D012995:Solubility