Preparation of in situ gel systems for the oral delivery of ibuprofen and its pharmacokinetics study in beagle dogs / 药学学报

ABSTRACT

The in situ gel systems can form gel in situ after administration to achieve sustained release, thus provides a promising strategy for drug delivery systems. The aim of this study was to design and prepare in situ gel systems for the oral delivery of ibuprofen (IBU-ISG) and study its pharmacokinetics in Beagle dogs. The characteristics of the basic material of gellan gum (Kelcogel, Kel) and sodium alginate (Manugel, M) were studied through investigating the complex viscosity of the Kel or M solution with or without different concentrations of calcium ion or sodium citrate to ascertain the amount range of the excipients. The measurement of complex viscosity of the solution (0. 5% Kel and 1% M) with different concentrations of sodium citrate and calcium ion was carried out to select the suitable proportion of calcium ion and sodium citrate. The formulation of binary IBU-ISG was optimized by monitoring the complex viscosity before gelling in vitro release property. The optimized formulation contains 1.0% sodium alginate, 0.5% gellan gum, 0. 21% sodium citrate and 0.056% calcium chloride. A single oral dose of IBU-ISG and reference formulation (IBU suspension) were given to each of the 6 healthy Beagle dogs, ibuprofen in plasma at different sampling times was determined by RP-HPLC. The pharmacokinetics parameters in 6 Beagle dogs were calculated. The Tmax of IBU-ISG and reference formulation were (1.8 +/- 0.6) and (0.4 +/- 0. 1) h. The Cmax values were (29.2 +/- 7.6) and (37.8 +/- 2.2) microg x mL(-1). The T(1/2) were (2.3 +/- 0.5) and (2.0 +/- 0.9) h, and the AUC(0-t) were (131.0 +/- 38.6) and (117.3 +/- 23.1) microg x mL(-1) x h, respectively. The binary IBU-ISG was successfully prepared.