Preparation and evaluation of dual-mode floating gastroretentive tablets containing itraconazole.
The aims of the present study were to prepare new dual-mode floating gastroretentive tablets (DF-GRT) containing itraconazole (ITR) and to evaluate influence of the dosage forms on pharmacokinetic parameters of ITR. The solubility of ITR was enhanced around 200 times (from 1.54 to 248.38 µg/mL) by preparing solid dispersion (SD) with hydroxypropylmethyl cellulose. Buoyancy of DF-GRT containing ITR-SD was established by both camphor sublimation and gas generation. Camphor sublimation decreased density of DF-GRT by making pores in tablet matrix, which led to elimination of lag time for floating. Carbon dioxide generated by sodium bicarbonate and citric acid helped to maintain buoyancy of DF-GRT. Therefore DF-GRT floated on the medium without lag time until disintegrated entirely during in vitro release study. They released 89.11% of the drug at 2 h. Residual camphor was <0.5 wt% after sublimation. The pharmacokinetics of DF-GRT was evaluated in six miniature pigs and compared to immediate release tablets (IRT). Mean AUC ratio of GRT/IRT was 1.36 but there was no statistical difference between AUC values. However delayed tmax, increased MRT and equivalent Cmax of DF-GRT supposed it could be a promising tool for gastroretentive drug delivery system containing ITR.
School of Pharmacy, Sungkyunkwan University , Suwon , Republic of Korea .
Ju-Young
JY
Kim
Yun-Seok
YS
Rhee
Chun-Woong
CW
Park
Jung-Myung
JM
Ha
Eun-Seok
ES
Park
D000818:Animals; D002164:Camphor / Q000097:blood / Q000138:chemical synthesis; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D017964:Itraconazole / Q000097:blood* / Q000138:chemical synthesis*; D012995:Solubility; D013552:Swine; D013556:Swine, Miniature; D013607:Tablets
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D013607:Tablets; D017964:Itraconazole; D002164:Camphor
Controlled release; gastro-floating system; miniature pigs; oral administration; porous matrix; site-specific drug delivery