[Preparation of in situ gel systems for the oral delivery of ibuprofen and its pharmacokinetics study in beagle dogs].
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.
Wu
Rui-ling
RL
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, China.
Zhao
Chun-shun
CS
Xie
Jing-wen
JW
Yi
Shao-ling
SL
Song
Hong-tao
HT
He
Zhong-gui
ZG
D000284:Administration, Oral; D000464:Alginates / Q000737:chemistry; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D002122:Calcium Chloride / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D003692:Delayed-Action Preparations; D004285:Dogs; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D007052:Ibuprofen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D000077559:Sodium Citrate; D014783:Viscosity
D000464:Alginates; D018712:Analgesics, Non-Narcotic; D002951:Citrates; D003692:Delayed-Action Preparations; D005079:Excipients; D006603:Hexuronic Acids; D011135:Polysaccharides, Bacterial; D000077559:Sodium Citrate; C048288:gellan gum; D020723:Glucuronic Acid; D002122:Calcium Chloride; D007052:Ibuprofen