Preparation, characterization, and in vivo evaluation of a self-nanoemulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex

Abstract

Background: As a poorly water-soluble drug, the oral application of morin is limited by its low oral bioavailability. In this study, a new self-nanoemulsifying drug delivery system (SNEDDS), based on the phospholipid complex technique, was developed to improve the oral bioavailability of morin.

Methods: Morin-phospholipid complex (MPC) was prepared by a solvent evaporation method and characterized by infrared spectroscopy and X-ray diffraction. After formation of MPC, it was found that the liposolubility of morin was significantly increased, as verified through solubility studies. An orthogonal design was employed to screen the blank SNEDDS, using emulsifying rate and particle size as evaluation indices. Ternary phase diagrams were then constructed to investigate the effects of drug loading on the self-emulsifying performance of the optimized blank SNEDDS. Subsequently, in vivo pharmacokinetic parameters of the morin-phospholipid complex self-nanoemulsifying drug delivery system (MPC-SNEDDS) were investigated in Wistar rats (200 mg/kg of morin by oral administration).

Results: The optimum formulation was composed of Labrafil(®) M 1944 CS, Cremophor(®) RH 40, and Transcutol(®) P (3:5:3, w/w), which gave a mean particle size of approximately 140 nm. Oral delivery of the MPC-SNEDDS exhibited a significantly greater C(max) (28.60 μg/mL) than the morin suspension (5.53 μg/mL) or MPC suspension (23.74 μg/mL) (all P < 0.05). T(max) was prolonged from 0.48 to 0.77 hours and to 1 hour for MPC and MPC-SNEDDS, respectively. In addition, the relative oral bioavailability of morin formulated in the MPC-SNEDDS was 6.23-fold higher than that of the morin suspension, and was significantly higher than that of the MPC suspension (P < 0.05).

Conclusion: The study demonstrated that a SNEDDS combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of morin.

Keywords: morin; oral bioavailability; phospholipid complex; self-nanoemulsifying drug delivery system.

Figure 1

Infrared spectra of (A) morin; (B) phospholipids; (C) morin-phospholipid complex; and (D) physical mixture of morin and phospholipids.

Figure 2

X-ray diffraction pattern of (A) morin; (B) phospholipids; (C) morinphospholipid complex; and (D) physical mixture of morin and phospholipids.

Figure 3

Ternary phase diagram of the SNEDDS formulation composed of the following: oil – Labrafil M 1944 CS; surfactant – Cremophor RH 40; and cosurfactant – Transcutol P, with a drug loading of 10%. Notes: The red outline represents the area explored for locating nanoemulsion region. The blue area represents nanoemulsion region.

Figure 4

Transmission electron microscope image of MPC-loaded SNEDDS formulation. Note: Scale bar = 200 nm. Abbreviations: MPC, morin-phospholipid complex; MPC-SNEDDS, morinphospholipid complex self-nanoemulsifying drug delivery system.

Figure 5

HPLC chromatographs of morin. Notes: (A) Blank plasma; (B) plasma containing morin; internal standard: benzoic acid. Abbreviation: HPLC, high performance liquid chromatography.

Figure 6

Plasma concentration-time curve after intravenous administration of morin in Wistar rats (n = 5) at a dose of 1 mg/kg.

Figure 7

Mean plasma concentration-time profiles of morin in Wistar rats (n = 5) after oral administration of morin, MPC, and MPC-SNEDDS formulation at a dose of 200 mg/kg. Abbreviations: MPC, morin-phospholipid complex; MPC-SNEDDS, morin-phospholipid complex self-nanoemulsifying drug delivery system.