Enhancing dissolution, serum concentrations and hypoglycemic effect of glibenclamide using solvent deposition technique.
OBJECTIVE
Glibenclamide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Therefore, to enhance the drug dissolution, serum concentrations and its hypoglycemic effects, it was formulated as solid dispersions and evaluated the relevant in vitro and in vivo parameters.


METHODS
The drug solid dispersions were prepared by solvent deposition technique using microcrystalline cellulose as the carrier in different ratios and their dissolution rates were compared to those of pure drug and its physical mixture with carrier. Drug serum concentrations and hypoglycemic effects in rabbits of pure drug, a physical mixture and the corresponding solid dispersion were investigated. In order to elucidate the observed in vitro and in vivo differences, IR spectroscopy and x-ray diffraction patterns of the formulations were studied.


RESULTS
The solid dispersion with the drug to carrier ratio of 1:19 showed the highest dissolution rate with the dissolution efficiency (DE) of 44.42 in comparison to pure drug (DE = 3.82), physical mixture (DE = 4.91) and other solid dispersions (DE between 13.85-39.94) and also produced higher drug serum concentrations (more than 4 times at 6th hour post dose) as well as enhanced hypoglycemic effects relative to pure drug and its corresponding physical mixture.


CONCLUSIONS
Solvent deposition technique was proved an effective tool of increasing dissolution probably due to enhanced wettability and reduced drug particle size, which in turn led to enhance drug serum concentrations and its hypoglycemic effects. Strong quantitative correlations were established between dissolution parameter and parameters related to serum concentrations as well as hypoglycemic effects.
Dastmalchi
Siavoush
S
Department of Medicinal Chemistry, School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
Garjani
Alireza
A
Maleki
Nasrin
N
Sheikhee
Golaleh
G
Baghchevan
Vida
V
Jafari-Azad
Parisa
P
Valizadeh
Hadi
H
Barzegar-Jalali
Mohammad
M
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D005905:Glyburide / Q000097:blood* / Q000138:chemical synthesis* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000097:blood* / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D012995:Solubility / Q000187:drug effects; D012997:Solvents / Q000138:chemical synthesis*; D013678:Technology, Pharmaceutical / Q000379:methods
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D012997:Solvents; D005905:Glyburide