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

Figures & data

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.

Table 1 Solubility of morin, MPC, and the physical mixture in water and n-octanol at room temperature

Sample	Solubility in water (μg/mL)a	Solubility in n-octanol (mg/mL)a
Morin	18.42 ± 1.49	11.96 ± 6.71
MPC	74.43 ± 0.36	>1000
Physical mixture	34.40 ± 0.01	13.85 ± 0.09

a Notes: Reported as mean ± standard deviation; n = 3.

Abbreviations: MPC, morin-phospholipid complex; the mixture of phospholipids and morin, physical mixture.

Table 2 Solubility of morin and MPC in different oils at room temperature

Type of oil	Solubility (mg/mL)
	MPCa	Morina
Lauroglycol™ FCC	20.40 ± 1.43	3.15 ± 0.056
Labrafil^® M 1944 CS	27.04 ± 1.38	5.83 ± 0.12
Lauroglycol 90	325.60 ± 52.31	83.30 ± 2.34

a Notes: Reported as mean ± standard deviation; n = 3.

Abbreviation: MPC, morin-phospholipid complex.

Table 3 Factors and levels of L₉ (3³) orthogonal test

Run	Oil	Surfactant	Cosurfactant
1	1 (3)	1 (3)	1 (1)
2	1 (3)	2 (4)	2 (2)
3	1 (3)	3 (5)	3 (3)
4	2 (4)	1 (3)	2 (2)
5	2 (4)	2 (4)	3 (3)
6	2 (4)	3 (5)	1 (1)
7	3 (5)	1 (3)	3 (3)
8	3 (5)	2 (4)	1 (1)
9	3 (5)	3 (5)	2 (2)

Notes: Orthogonal experimental form of L₉ (3³) was adopted to determine the ratios of oil, surfactant, and cosurfactant to be evaluated to a self-nanoemulsifying drug delivery system (SNEDDS) formulation.

Table 4 Droplet size and polydispersity index of SNEDDS formulations after dilution with distilled water at a ratio of 1:100

System	Ratio	Particle size (nm)a	Polydispersity indexa	Time of emulsification
Labrafil^® M 1944 CS/Cremophor^® EL/Transcutol^® P	3:3:1	35.21 ± 0.79	0.111 ± 0.016	1 min~3 min
	3:4:2	28.73 ± 0.61	0.098 ± 0.013	<1 min
	3:5:3	28.34 ± 0.56	0.067 ± 0.006	<1 min
	4:3:2	33.85 ± 1.21	0.082 ± 0.006	<1 min
	4:4:3	36.92 ± 1.94	0.222 ± 0.031	1 min~3 min
Labrafil M 1944 CS/Cremophor RH 40/Transcutol P	3:3:1	39.93 ± 0.87	0.099 ± 0.013	<1 min
	3:4:2	30.48 ± 0.74	0.141 ± 0.019	<1 min
	3:5:3	28.34 ± 0.03	0.079 ± 0.003	<1 min
	4:3:2	39.45 ± 1.17	0.093 ± 0.009	<1 min
	4:5:1	29.93 ± 0.92	0.114 ± 0.017	1 min~3 min
	4:4:3	37.20 ± 0.63	0.228 ± 0.039	<1 min
	5:4:1	43.59 ± 1.85	0.101 ± 0.008	1 min~3 min
	5:3:3	76.75 ± 2.16	0.243 ± 0.011	1 min~3 min
Lauroglycol™ FCC/Cremophor RH 40/Transcutol P	3:3:1	35.69 ± 1.22	0.288 ± 0.039	<1 min
	3:4:2	34.38 ± 0.97	0.101 ± 0.020	<1 min
	3:5:3	32.45 ± 1.13	0.253 ± 0.041	<1 min
	4:4:3	41.93 ± 1.52	0.088 ± 0.002	<1 min
Lauroglycol FCC/Tween^® 80/1, 2-propylene glycol	4:4:3	37.93 ± 2.90	0.228 ± 0.027	<1 min
Lauroglycol FCC/Cremophor EL/Transcutol P	3:3:1	57.17 ± 2.03	0.388 ± 0.046	>3 min
Labrafil M 1944 CS/Tween 80/Transcutol P	3:5:3	97.40 ± 4.58	0.267 ± 0.031	<1 min

a Notes: Reported as mean ± standard deviation; n = 3.

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.

Table 5 Bioavailability and pharmacokinetic parameters (mean ± standard deviation) of morin in Wistar rats after oral administration of morin, MPC, and MPC-SNEDDS at a dose of 200 mg/kg (n = 5)

	Intravenous morin (1 mg/kg)	Oral morin	Oral MPC	Oral MPC-SNEDDS
AUC0-t (mg/L h)	11.89 ± 0.21	10.64 ± 1.9	57.64 ± 17.19**	76.91 ± 23.77**,##
MRT0-t (h)	1.33 ± 0.32	1.91 ± 0.28	1.87 ± 0.18	2.12 ± 0.01#
Tmax (h)	0.05 ± 0.00	0.48 ± 0.17	0.77 ± 0.27*	1.00 ± 0.47**,#
Cmax (μg/mL)	13.86 ± 3.91	5.53 ± 2.07	23.74 ± 3.87**	28.60 ± 9.25**,#
Fa (%)	100.00	0.45	2.42	3.24
Fr (%)	–	100	541.73	722.84

* Notes: P < 0.05 compared with morin group;

** P < 0.01 compared with morin group;

# P < 0.05 MPC-SNEDDS group compared with MPC group;

## P < 0.01 MPC-SNEDDS compared with MPC group.

Abbreviations: F_a, absolute bioavailability; MRT, mean retention time; MPC, morin-phospholipid complex; MPC-SNEDDS, morin-phospholipid complex self-nanoemulsifying drug delivery system; F_r, relative bioavailability.

Figure 5 HPLC chromatographs of morin.

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.

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.

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.