Co-solvent solubilization of some poorly-soluble antidiabetic drugs

Abstract

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.

Solubility of Gliclazide in Transcutol + Water Co-solvent Mixtures at (298.15 to 333.15) K

“…The mole fraction solubility of GLZ in pure water at 298.15 and 310.15 K has been reported as < 2.23 × 10 -6 and 3.06 × 10 -6 , respectively. 3,5 However, in present study the mole fraction solubility of GLZ in pure water at 298.15 and 308.15 K was observed as 1.9 × 10 -6 and 2.84 × 10 -6 , respectively which were very close to reported values (Table 2). Based on these results, GLZ has been considered as practically insoluble (poorly soluble) in pure water and soluble in pure Transcutol.…”

“…1,2 It is a second generation hypoglycemic agent which is prescribed in the treatment of type 2 diabetes mellitus. [1][2][3][4] It is very poorly soluble drug according to the biopharmaceutical classification system (BCS) of drugs (BCS class II) due to which its dissolution is poor. 2,4 Poor solubility and dissolution often resulted in poor in vivo absorption of such drugs.…”

“…Co-solvent approach has also been applied to enhance aqueous solubility of seven poorly soluble antidiabetic drugs including GLZ. 3 Co-solvent technique is error free approach which is usually applied for solubilization as well as stabilization of drugs/pharmaceuticals in aqueous solutions. 15,16 Solubility is one of the important Figure 1.…”

“…1,2,4 The aqueous solubility of GLZ at 25 and 37 °C has been reported as < 40 and 55 µg ml -1 , respectively. 3,5 Various approaches such as surfactants, 5 solid dispersions, 1,4,[6][7][8][9][10] micronization, 11,12 ordered mixing, 2 co-grinding 13 and cyclodextrins complexation 14 have been applied to enhance solubility and dissolution rate of GLZ. Co-solvent approach has also been applied to enhance aqueous solubility of seven poorly soluble antidiabetic drugs including GLZ.…”

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique

“…However, the drawback for the use of GM as oral dosage forms is attributable to its low aqueous solubility (1.6 µg/mL) and slow dissolution rate, which lead to low oral bioavailability. 6,7 Hence many studies have tried to enhance its solubility, and several reports including those where nanocrystals, 8 cosolvency, 9 spray congealing, 10 solid self-nanoemulsify,…”