Mechanisms of microemulsion enhancing the oral bioavailability of puerarin: comparison between oil-in-water and water-in-oil microemulsions using the single-pass intestinal perfusion method and a chylomicron flow blocking approach

Figures & data

Table 1 Formulations and droplet sizes of microemulsions and puerarin content

Formulations				Composition (%, w/w)	Droplet size		Puerarin content (mg/mL)
Rx	Oil	S	Co-S	Oil:S:Co-S:W	Mean (nm)	PDI
O/W-ME	Ethyl oleate	Cremophor RH40	Propylene glycol	2.1:12.6:6.3:79.0	13.50 ± 0.58	0.098 ± 0.008	11.32 ± 0.16
W/O-ME	Ethyl oleate	Lecithin	Ethanol	35.7:26.9:26.7:10.7	24.04 ± 1.02	0.102 ± 0.013	23.14 ± 0.32

Note: Each value is the mean ± standard deviation of three separate determinations.

Abbreviations: Co-S, co-surfactant; ME, microemulsion; O, oil; PDI, polydispersity index; S, surfactant; W, water; w, weight; Rx, prescription.

Figure 1 Pseudo ternary phase diagrams composed of (A) O/W-ME: Cremophor RH40 and propylene glycol as surfactant and co-surfactant (2:1, w/w), (B) W/O-ME: lecithin and ethanol as surfactant and co-surfactant (1:1, w/w), while ethyl oleate was used as the oil phase. The grey area represents the ME existence range.

Abbreviations: Co-S, co-surfactant; ME, microemulsion; O, oil; S, surfactant; W, water; w, weight.

Figure 2 Transmission electron microscopy analysis of microemulsions: (A) O/W-ME and (B) W/O-ME.

Note: Scale bar: 100 nm.

Abbreviations: Me, microemulsion; O, oil; W, water.

Figure 3 The K_a obtained for in situ perfusion in the SPIP model for four different intestinal segments. The data are presented as the mean ± SD (n=6).

Abbreviations: K_a, absorption rate constant; ME, microemulsion; min, minute; O, oil; SD, standard deviation; SPIP, single-pass intestinal perfusion; W, water.

Figure 4 The P_app obtained for in situ perfusion in the SPIP model for four different intestinal segments. The data are presented as the mean ± SD (n=6).

Abbreviations: P_app, apparent permeability coefficients; ME, microemulsion; min, minute; O, oil; SD, standard deviation; SPIP, single-pass intestinal perfusion; W, water.

Figure 5 The K_a obtained for in situ perfusion in the SPIP model for the suspension, O/W-ME and W/O-ME. The data are presented as the mean ± SD (n=6).

Abbreviations: K_a, absorption rate constant; ME, microemulsion; min, minute; O, oil; SD, standard deviation; SPIP, single-pass intestinal perfusion; W, water.

Figure 6 The P_app obtained for in situ perfusion in the SPIP model for the suspension, O/W-ME and W/O-ME. The data are presented as the mean ± SD (n=6).

Abbreviations: P_app, apparent permeability coefficients; ME, microemulsion; min, minute; O, oil; SD, standard deviation; SPIP, single-pass intestinal perfusion; W, water.

Table 2 Pharmacokinetic parameters obtained following the oral administration of puerarin microemulsions and a puerarin suspension in a single dose of 100 mg/kg to cycloheximide- and saline-treated rats (n=6, mean ± standard deviation)

Pharmacokinetic parameters	Cycloheximide treated rats			Saline treated rats
	O/W-ME	W/O-ME	Suspension	O/W-ME	W/O-ME	Suspension
AUC (μg h/mL)	2.415 ± 0.279*	3.600 ± 0.425*	1.837 ± 0.317*	5.335 ± 1.646#	5.636 ± 1.358#	2.895 ± 0.527
Cmax (μg/mL)	0.468 ± 0.098*	0.618 ± 0.102*	0.408 ± 0.048	1.029 ± 0.208	1.966 ± 0.362	0.740 ± 0.099
Tmax (h)	0.750 ± 0.158	0.931 ± 0.731	0.361 ± 0.323	0.792 ± 0.436	0.611 ± 0.430	0.444 ± 0.086

Notes:

* P<0.05 versus saline treated rats as the control

# P<0.05 versus suspension in saline treated rats.

Abbreviations: AUC, area under the curve; C_max, maximum concentration; h, hour; ME, microemulsion; O, oil; T_max, time of maximum concentration; W, water.

Figure 7 The whole blood concentration versus time profiles of puerarin after intragastric administration in the form of (A) an O/W-ME, (B) a W/O-ME, and (C) a suspension at a dose of 100 mg/kg to cycloheximide- and saline-treated rats (n=6).

Abbreviations: h, hours; ME, microemulsion; O, oil; W, water.