Formulation and evaluation of luteolin supersaturatable self-nanoemulsifying drug

The current investigation was aimed to enhance the solubility and oral bioavailability of luteolin by employing the supersaturable self-nanoemulsifying drug delivery system(S-SNEDDS). The formulation for SNEDDS consisted of caprylic/capric triglyceride, polyoxyl 35 hydrogenated castor oil and polyethylene glycol 400 in a ratio of 20.1:48.2:31.7 by weight, which was determined and optimized based on solubility studies, pseudo-ternary phase diagrams and central composite design. Hydroxypropyl methylcellulose (HPMC) K4M at a 2% mass ratio was determined to be the optimal precipitation inhibitor for luteolin-loaded SNEDDS according to in vitro precipitation experiments.

Luteolin S-SNEDDS formed clarified nanoemulsion with a particle size of 25.60 nm and a zeta potential of −10.2 mV after dilution. The interaction between luteolin and HPMC K4M was measured by powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy and ¹H NMR spectroscopy. Moreover, S-SNEDDS achieved an excellent in vitro dissolution of 99% in phosphate buffer at pH 6.8 with 0.5% Tween 80. The in vivo pharmacokinetics study of S-SNEDDS showed a significant increase (2.2-fold) in the oral bioavailability of luteolin in rats compared to that of the conventional SNEDDS. In summary, these observations illustrated the application prospects of S-SNEDDS technology in promoting solubility and oral bioavailability from poorly water-soluble drugs, at least for luteolin.

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Author links open overlay panelNanZhang, FeiZhang, ShuoXu, KaiqingYun, WenjingWu, WeisanPan
Journal of Drug Delivery Science and Technology
https://doi.org/10.1016/j.jddst.2020.101783

Keywords: Luteolin, Supersaturatable self-nanoemulsifying drug delivery system, Precipitation inhibitor, Oral bioavailability