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  • Title: Preparation and evaluation of self-nanoemulsified drug delivery systems (SNEDDSs) of matrine based on drug-phospholipid complex technique.
    Author: Ruan J, Liu J, Zhu D, Gong T, Yang F, Hao X, Zhang Z.
    Journal: Int J Pharm; 2010 Feb 15; 386(1-2):282-90. PubMed ID: 19961910.
    Abstract:
    To enhance oral bioavailability of matrine, a dedicated and newly emerging drug system called self-nanoemulsifying drug delivery system (SNEDDSs) was developed. Phospholipid complex (MPC) was prepared using solvent-evaporation method to improve the liposolubility of matrine. Solubilization test, infrared spectroscopy (IR) and differential scanning calorimetry (DSC) analysis were employed to confirm the formation of MPC. A rational experimental design was adopted to optimize the properties of SNEDDSs. Eight SNEDDSs prototypes were obtained to form nanoemulsion spontaneously based on optimization experiments. Among them, MPC prepared exhibited excellent solubility. SNEDDSs 2 (composition: Lauroglycol FCC, Cremophor EL and Transcutol HP; ratio: 6:4:1) was selected as the optimal formulation, with a mean droplet size in the range of 65-80 nm and 8.34% of the leakage rate, exhibiting instantaneous emulsion formation with only one flask inversion. Media pH and dilution factor showed no effect on the droplet size. The oral absorption of matrine in rats via SNEDDSs delivery was investigated. C(max) was increased dramatically from 4.12 to 6.52 and 7.95 microg/mL in case of matrine, MPC and MPC-SNEDDS. In parallel to C(max), prolonged T(max) from 0.39 to 0.50h, and 3.00 h could be observed. AUC(0-t) of MPC-SNEDDSs was significantly higher than other two counterparts. In conclusion, the absolute bioavailability of matrine drastically increased from 25% to 84.6% by the formation of MPC-SNEDDS, with an outstanding relative bioavailability of 338%, suggesting its great potential for clinical application.
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