Bioavailability of immediate- and extended-release formulations of glipizide in healthy male volunteers.
OBJECTIVE
An extended-release glipizide formulation using a hydrophilic matrix system containing hydrophilic polymers has been developed for use in diabetes mellitus. This study compared the pharmacokinetic parameters of immediate- and extended-release formulations of glipizide 5mg in healthy male volunteers.


METHODS
In a single-dose, four-period, four-treatment, Latin-square crossover study, the bioavailability of immediate-release glipizide 5mg (Glynase) [GL], extended-release glipizide 5mg (Glynase) XL [GLXL], Glucotrol XL [GTXL], and the new formulation developed in our laboratory [GLPF]) was compared. Plasma glipizide levels of the four formulations were determined at different time intervals, and pharmacokinetic parameters were analysed using a two-compartment body model.


RESULTS
The mean peak plasma concentration (C(max)) of the immediate-release formulation (523+/-60 ng/mL) was significantly higher (p<0.05) than those of the three extended-release formulations (403+/-24, 349+/-37 and 426+/-55 ng/mL for GLXL, GTXL and GLPF, respectively). Mean time to reach C(max) was 1.83+/-0.3 hours for GL, 4.41+/-1.2 hours for GLXL, 3.21+/-0.8 hours for GTXL and 3.24+/-0.4 hours for GLPF. The order of magnitude of area under the plasma concentration-time curve was GTXL (5591 ng . h/mL)>GLXL (4,771 ng . h/mL)>GLPF (4,537 ng . h/mL)>GL (1,897 ng . h/mL). The mean residence time was 3.14+/-0.59 hours for GL, 8.26+/-0.81 hours for GLXL, 9.70+/-2.70 hours for GTXL and 7.87+/-1.93 hours for GLPF. Extended-release glipizide formulations maintained effective plasma drug concentrations for approximately 24 hours. Plasma levels of glipizide fluctuated less with GTXL than with the other two extended-release formulations.


CONCLUSIONS
The newly developed formulation (GLPF) maintained effective levels of glipizide for a period of more than 20 hours, with quicker onset of action than the other two formulations. This formulation may be more economical than glipizide GITS.
Dhawan
Sanju
S
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India. sanjudhawan@rediffmail.com
Singh
Bhupinder
B
Garg
Santosh Kumar
SK
Hota
Debasish
D
Dash
Radharaman Jiban
RJ
Singla
Anil Kumar
AK
Sinha
Vivek Ranjan
VR
D000293:Adolescent; D000328:Adult; D000465:Algorithms; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005913:Glipizide / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D005913:Glipizide