科研之友
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摘要
Glipizide (GPZ) has been widely used in the treatment of type-2 diabetics as insulin secretogague. Multiunit chitosan based GPZ floating microspheres was prepared by ionotropic gelation method for gastroretentive delivery using sodiumtripolyphosphate as cross-linking agent. Pharmacokinetic study of microspheres was done in rabbit and plasma samples were analyzed by a newly developed and validated high-performance liquid chromatographic method. Method was developed on Hypersil ODS-18 column using a mobile phase of 10mM phosphate buffer (pH, 3.5) and methanol (25:75, v/v). Elute was monitored at 230nm with a flow rate of 1 mL/min. Calibration curve was linear over the concentration range of 25.38-2046.45 ng/mL. Retention times of GPZ and internal standard (gliclazide) were 7.32 and 9.02 mm respectively. Maximum plasma drug concentration, area under the plasma drug concentration-time curve and elimination half life for GPZ floating microspheres were 2.88 +/- 0.29 mu gmL(-1), 38.46 +/- 2.26 mu gh mL(-1) and 13.55 +/- 1.36 h respectively. When the fraction of drug dissolved from microspheres in pH 7.4 was plotted against the fraction of drug absorbed, a linear correlation (R-2 = 0.991) was obtained in in vitro and in vivo correlation study.
- 出版日期2014-4
