In vitroandin vivostudies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier

Abstract

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.

Repaglinide-loaded nanostructured lipid carriers with different particle sizes for improving oral absorption: preparation, characterization, pharmacokinetics, and in situ intestinal perfusion

“…Repaglinide could be absorbed well in the four intestinal segments from the result of repaglinide solution (REP-Sol), which was consistent with the feature of BCS II drug and determining results of P eff values using SPIP method in rats for high-permeability compound (Zakeri-Milani et al, 2005). The K a and P eff values of duodenum and jejunum were significantly better than those of ileum and colon for REP-Sol, which was corresponding with Yin et al (2012). The K a and P eff values of REP-NLC-Small size showed significant difference and improvement in the jejunum (p < .05), ileum (p < .01) and colon (p < .01) compared with REP-Sol.…”

Improvement in oral bioavailability and dissolution of tanshinone IIA by preparation of solid dispersions with porous silica

“…The others effects, such as hydrogen bonding between the silanol groups of silica and carbonyl groups of tanIIA were demonstrated using FTIR spectroscopy. Hydrogen‐bond formation could improve the wettability properties of the drug and further increase drug dissolution rates [39–41]…”

Bilayer Matrix Tablets for Prolonged Actions of Metformin Hydrochloride and Repaglinide

“…RG belonged to a BCS II drug with low aqueous solubility and high permeability, thus, its absorption enhancement was obtained by increasing the dissolution rate. A previous report indicated that its bioavailability was increased up to 2.2 folds by solid dispersion; moreover, the absorption predominantly occurred in the upper gastrointestinal tract, especially in the segment of the duodenum and jejunum (15). On the other side, it was observed that the values of MH AUC obtained from the IR and SR tablets were equal, whereas the absorption of MH was site-dependent and the drug was mainly absorbed in the proximal small intestine (31,32).…”

“…Due to the presence of amorphous form, the solubility and bioavailability were enhanced greatly (15). Thus, the active ingredient of solid dispersion of RG/PVP K30 was formulated into the tablets.…”

“…To enhance the drug solubility, a solid dispersion of RG/ PVP K30 (Table I) with the ratio of 1:10 (w/w) was prepared before the granulation process (15).…”