Implication of inclusion complexation of glimepiride in cyclodextrin-polymer systems on its dissolution, stability and therapeutic efficacy.
The effect of complexation of glimepiride, a poorly water-soluble antidiabetic drug, with beta-cyclodextrin and its derivatives (HP-beta-CyD and SBE-beta-CyD) in presence of different concentrations of water-soluble polymers (HPMC, PVP, PEG 4000 and PEG 6000) on the dissolution rate of the drug has been investigated. The results revealed that the dissolution rate of the drug from these ternary systems is highly dependent on polymer type and concentration. The dissolution rate of the drug from ternary systems containing PEG 4000 or PEG 6000 seems to be generally higher than from systems containing HPMC or PVP. An optimum increase in the dissolution rate of the drug was observed at a polymer concentration of 5% for PEG 4000 or PEG 6000 and at 20% concentration of HPMC or PVP. The dissolution rate of the drug from the ternary system glimepiride-HP-beta-CyD-5% PEG 4000 was high compared to the other systems. Tablets containing the drug or its equivalent amount of this ternary system were prepared and subjected to accelerated stability testing at 40 degrees C/75% R.H. to investigate the effect of storage on the chemical stability as well as therapeutic efficacy of the tablets. The results revealed stability of the tablets and consistent therapeutic efficacy on storage.
Ammar
H O
HO
Department of Pharmaceutical Technology, National Research Center, Dokki, Cairo, Egypt. husseinammar@hotmail.com
Salama
H A
HA
Ghorab
M
M
Mahmoud
A A
AA
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D065347:Hypromellose Derivatives; D007700:Kinetics; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013453:Sulfonylurea Compounds / Q000737:chemistry*; D013607:Tablets; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011108:Polymers; D013453:Sulfonylurea Compounds; D013607:Tablets; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; C057619:glimepiride; D008747:Methylcellulose; D011205:Povidone