Self-Emulsifying Drug Delivery Systems for Improving Oral Absorption of Ginkgo Biloba Extracts

Figures & data

TABLE 1  Vehicle compositions of the designed SEDDS formulations

Formula 1		Formula 2
Oil	Miglyol 812	Miglyol 812
Surfactant	Tween 80	Tween 80-Cremophor (1:1)	EL 35
Cosolvent	1, 2-Propanediol	1, 2-Propanediol
Formula 3		Formula 4
Oil	Ethyl oleate	Ethyl oleate
Surfactant	Tween 80	Tween 80-Cremophor (1:1)	EL 35
Cosolvent	1, 2-Propanediol	1, 2-Propanediol

TABLE 2  Solubility of Ginkgo biloba extracts in various vehicles at 25°C (n = 3, mg/g)

	Solubility
Vehicle	Flavonol glycosides	Bilabolide	Ginkgolide A	Ginkgolide B	Ginkgolide C	Terpene lactones
Water	85.8 ± 3.6	14.4 ± 0.6	1.9 ± 0.8	0.4 ± 0.1	1.5 ± 0.3	18.2 ± 0.4
1,2-Propanediol	135.3 ± 5.8	24.5 ± 1.0	8.7 ± 0.6	4.3 ± 0.2	5.1 ± 0.2	42.7 ± 0.9
Glycerol	120.4 ± 3.3	25.8 ± 1.1	8.5 ± 0.4	4.8 ± 0.3	5.5 ± 0.3	44.5 ± 1.2

FIG. 1  Pseudoternary phase diagrams indicating the efficient self-emulsification region with Miglyol 812 as oil. (A) Tween 80 as surfactant; (B) Tween 80-Cremophor EL 35 (1:1) as the mixed surfactants (Key: The region of efficient self-emulsification is bound by the solid line; and the filled squares represent the composition evaluated.)

FIG. 2  Pseudoternary phase diagrams indicating the efficient self-emulsification region with ethyl oleate as oil. (A) Tween 80 as surfactant; (B) Tween 80-Cremophor EL 35 (1:1) as the mixed surfactants (Key: The region of efficient self-emulsification is bound by the solid line; and the filled squares represent the composition evaluated.)

FIG. 3  Dissolution profiles of flavone glycosides, bilobalide, ginkgolide A, ginkgolide B, and ginkgolide C from SEDDS (•) and the conventional tablets (○). (A) Flavone glycosides; (B) bilabolide; (C) ginkgolide A; (D) ginkgolide B; (E) ginkgolide C. Tests were conducted in 100 ml of water at 37 ± 0.5°C with a rotation speed of 100 r/min. Each value is the mean ± SD (n = 3).

FIG. 4  Bilabolide plasma concentration-time profiles for either SEDDS (•) or tablets (○) following oral administration at a single dose of 800 mg GBE in dogs. Each value is the mean ± SE (n = 6).

FIG. 5  Ginkgolide A plasma concentration-time profiles of either SEDDS (•) or tablets (○) following oral administration at a single dose of 800 mg GBE in dogs. Each value is the mean ± SE (n = 6).

FIG. 6  Ginkgolide B plasma concentration-time profiles of either SEDDS (•) or tablets (○) following oral administration at a single dose of 800 mg GBE in dogs. Each value is the mean ± SE (n = 6).

TABLE 3  Main pharmacokinetic parameters of bilabolide, ginkgolide A and ginkgolide B after a single oral dose of Ginkgobiloba extract 800 mg SEDDS and tablets in dogs

Parameters	Unit	SEDDS	Tablets
Bilabolide
Cmax	ng/ml	201.19 ± 38.81	138.99 ± 57.90
Tmax	hr	1.58 ± 0.34	2.33 ± 0.75
ke	hr^−1	0.410 ± 0.080	0.511 ± 0.131
t1/2	hr	1.74 ± 0.33	1.45 ± 0.45
AUC0 → 10 h	ng/ml·hr	727.0 ± 276.8	466.9 ± 182.9
F	%	162.1 ± 42.5	100
Ginkgolide A
Cmax	ng/ml	252.60 ± 90.93	165.76 ± 37.44
Tmax	hr	1.50 ± 0.47	2.42 ± 0.92
ke	hr^−1	0.512 ± 0.163	0.558 ± 0.216
t1/2	hr	1.50 ± 0.48	1.42 ± 0.60
AUC0 → 10 h	ng/ml·hr	839.9 ± 244.2	565.4 ± 93.6
F	%	154.6 ± 65.3	100
Ginkgolide B
Cmax	ng/ml	44.89 ± 15.29	31.09 ± 6.98
Tmax	hr	1.46 ± 0.40	2.25 ± 0.88
ke	hr^−1	0.284 ± 0.119	0.344 ± 0.193
t1/2	hr	2.75 ± 0.92	2.69 ± 1.66
AUC0 → 10 h	ng/ml·hr	164.7 ± 54.3	104.6 ± 28.2
F	%	155.8 ± 26.8	100

Mean ± SE, n = 6, *p < 0.05.