Preparation, Characterization, and In Vivo Evaluation of Gentiopicroside-Phospholipid Complex (GTP-PC) and Its Self-Nanoemulsion Drug Delivery System (GTP-PC-SNEDDS)

Abstract

The objective of the present study was to develop a gentiopicroside-phospholipid complex (GTP-PC) and its self-nanoemulsion drug delivery system (GTP-PC-SNEDDS) to increase the oral bioavailability of gentiopicroside (GTP). The factors affecting the formation of GTP-PC were studied with the complexation efficiency and dissociation rate. The properties of the complex were investigated by means of differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectra (FT-IR), dissolution, etc. Then, GTP-PC was loaded into SNEDDS by investigating the effects of weight ratios of GTP-PC to blank SNEDDS, preparation technology, dilution media, and dilution multi, based on the screening results of oils, surfactants, and cosurfactants. In rats, GTP, GTP-PC, and GTP-PC-SNEDDS were orally administered at different times, and GTP concentrations were determined using RP-HPLC. The optimal GTP-PC was prepared with tetrahydrofuran as the reaction solvent, GTP:phospholipid = 1:2, and stirring for 4 h. The optimal prescription for GTP-PC-SNEDDS was as follows: Maisin 35-1:Miglycol = 30%, Labrasol:Cremophor EL = 1:4 = 40%, Transcutol P = 30%; Maisin 35-1:Miglycol = 12, and the ratio of GTP-PC to blank was 1:10—then the mixture was stirred at 37 °C for 1 d and then placed for 2 d to form stable GTP-PC-SNEDDS. After oral administration of GTP, GTP-PC and GTP-PC-SNEDDS, and mean plasma GTP concentration–time curves were all in accordance with the single-compartment model. The Cmax, AUC0–∞, and Fr of the three formulations were significantly higher than that of GTP, demonstrating that GTP was metabolized rapidly, and its higher bioavailability could be achieved by the formation of GTP-PC and GTP-PC-SNEDDS. Among the three formations, the bioavailability of GTP-PC-SNEDDS was highest, with approximately 2.6-fold and 1.3-fold of Fr value, compared with GTP-PC (suspension) and GTP-PC (oil solution), respectively. Compared with GTP, GTP-PC and GTP-PC-SNEDDS enhanced the bioavailability of GTP significantly. In the future, this study could serve as a reference for clinical trials using GTP-PC and GTP-PC-SNEDDS.

Keywords

• gentiopicroside
• phospholipid complex
• self-nanoemulsion drug delivery system
• oral bioavailability
• pharmacokinetics