Co-solvent solubilization of some poorly-soluble antidiabetic drugs.
Co-solvent solubilization approach has been used to enhance the solubility of seven antidiabetic drugs: gliclazide, glyburide, glipizide, glimepiride, repaglinide, pioglitazone, and roziglitazone. Solubility in water, phosphate buffer (pH 7.4), six co-solvent solutions prepared in water as well as phosphate buffer (pH 7.4) and pH-solubility profile of various drugs have been determined at 25 degrees C. Aqueous solubility of various drugs was found to be less than 0.04 mg/mL. Solubility of gliclazide, glipizide and repaglinide increased by 3-6 times by using phosphate buffer (pH 7.4) as solvent. Solubility enhancement by pH modification was not sufficient. Significant enhancement in solubility could be achieved by the use of co-solvents. The combined effect of co-solvent and buffer was synergistic and enormous increase in solubility of sulfonylureas and repaglinide could be achieved. In the case of glitazones, however, co-solvent alone caused significant enhancement; the presence of buffer had negative effect on the solubilization potential of the co-solvents. Up to 763, 316, 153, 524, 297, 792 and 513 times increase in solubility could be achieved in the case of gliclazide, glyburide, glimepiride, glipizide, repaglinide, pioglitazone and rosiglitazone, respectively.
Seedher
Neelam
N
Department of Chemistry, Panjab University, Chandigarh, India. nseedher@yahoo.com
Kanojia
Mamta
M
D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000737:chemistry*; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
D007004:Hypoglycemic Agents; D010710:Phosphates; D012997:Solvents; D014867:Water