Improvement of the dissolution behavior of gliclazide, a slightly soluble drug, using solid dispersions

Gliclazide is a second generation sulphonylurea used in the treatment of type 2 diabetes characterized by a low risk of hypoglycaemia and cardiovascular disorders. This drug shows poor water solubility, particularly at low pH values, that may cause reduced and variable absorption after oral administration, above all in fasted state. To improve gliclazide dissolution behavior, different drug carrier systems were prepared and tested using two different methods: co-mixing and co-milling. The samples produced were characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron mi- croscopy. Their dissolution rate was tested and compared to an immediate release commercial product. Several approaches were effective for a rapid and complete dissolution of this drug: co-milling with suitable hydrophilic carriers such as cross-linked swellable polymers or amorphous silica and co-milling with a small amount of sodium lauryl sulphate (10 mg). In the case of the highest dose (80 mg) both approaches should be used at the same time to avoid saturation of the medium.