Role of nitric oxide in angiotensin IV-induced increases in cerebral blood flow

Whether a rapid elevation of serum gliclazide concentration in human subjects can be achieved through an acceleration of dissolution of gliclazide from a formulation was examined. A soft gelatin capsule containing PEG 400, PEG 4000, Tween 20 and glycerin was prepared as a formulation that may accelerate dissolution of gliclazide. The in vitro dissolution of gliclazide at pH 7.2 was identical for the soft capsule and conventional tablets, Diamicron and Diberin. However, at pH 1, 2 and 4.0 the dissolution from the soft capsule was more rapid compared to the tablets. When bioavailability parameters were compared following oral administration of the soft capsule and Diamicron to 16 healthy Korean male subjects, the parameters representing the amount of adsorption (i.e. the area under the serum gliclazide concentration vs. time curve up to 24 h, AUC24, and the peak serum concentration Cmax) were not statistically different for both formulations. However, the time required to reach the peak (Tmax) was significantly shorter for the soft capsule than for the Diamicron. Our results, therefore, indicate that a rapid elevation of serum gliclazide concentration following oral administration of a formulation can be achieved by accelerating the in vitro dissolution of gliclazide from the formulation into the acidic buffers. Thus, the rate of gastrointestinal absorption of gliclazide appears to be dependent on its in vivo dissolution rate in gastric fluid. A soft capsule containing a PEG 400 suspension of gliclazide appears to be an appropriate formulation for accelerating the dissolution.