In vitro and in vivo evaluation of two extended release preparations of combination metformin and glipizide.
A system that can deliver multi-drugs at a prolonged rate is very important to the treatment of various chronic diseases such as diabetes, asthma, and heart disease. Two controlled-release systems, which exhibited similar release profiles of metformin and glipizide, i.e., elementary osmotic pump tablets (EOP) and bilayer hydrophilic matrix tablet (BT), were designed. The effects of pH and hydrodynamic conditions on drug release from two formulations were investigated. It was found that both drug releases from EOP were not sensitive to dissolution media pH and hydrodynamics change, while the release of glipizide from BT was influenced by the stirring rate. Moreover, in vivo evaluation was performed, relative to the equivalent dose of conventional metformin tablet and glipizide tablet, by a three-crossover study in six Beagle dogs. Cumulative percent input in vivo was compared to in vitro release profiles. The linear correlations of metformin and glipizide between fraction absorbed in vivo and fraction dissolved in vitro were established for EOP-a true zero-order release formula, whereas only nonlinear correlations were obtained for BT. In conclusion, drug release from EOP was both independent of in vitro and in vivo conditions, where the best sustained release effect was achieved, whereas the in vitro dissolution test employed for BT needed to be further optimized to be biorelevant.
Defang
Ouyang
O
Department of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. ouyangdf@21cn.com
Shufang
Nie
N
Wei
Li
L
Hong
Guo
G
Hui
Liu
L
Weisan
Pan
P
D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D004338:Drug Combinations; D005913:Glipizide / Q000737:chemistry / Q000493:pharmacokinetics*; D007004:Hypoglycemic Agents / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D008687:Metformin / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D009995:Osmosis; D012995:Solubility; D013607:Tablets
D003692:Delayed-Action Preparations; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D013607:Tablets; D008687:Metformin; D005913:Glipizide