In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.
A combination therapy of metformin hydrochloride (MH) and repaglinide (RG) achieves a perfect glycemic control; however, the combination formulation of immediate release must be taken several times a day, compromising the therapeutic benefits and causing inconveniences to the patients. Herein, a bilayer matrix tablet that aimed at continuously releasing both MH and RG over time was developed, in which the two drugs were formulated into two separated layers. The tablets were prepared by wet granulation method, and the optimized formulation was obtained by evaluating the factors that affected the drug release. The bilayer tablets simultaneously released the two drugs over 12 h; and a better in vivo performance with a steady plasma concentration, markedly lower Cmax, prolonged Tmax, and perfect absorption was obtained. Summarily, the bilayer matrix tablets sustained both MH and RG release over time, thereby prolonging the actions for diabetic therapy and producing better health outcomes.
Statistical analysis indicated that the capsules containing Surelease-coated pellets had a satisfactory sustained-release behavior and a desired pharmacokinetic property.
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