Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation

Figures & data

Figure 1 Chemical structure of 20(S)-25-OCH₃-PPD.

Table 1 Parameters of mass spectrometry conditions for analysis of the analytes

Parameters
Ion spray voltage	4,000 V
Ion source temperature	400°C
Ion source gas 1	40 psi
Ion source gas 2	40 psi
Curtain gas	10 psi
Collision gas	6 psi

Table 2 Solubility of 25-OCH₃-PPD in various oily phases, surfactants, and cosurfactants

Vehicles	Solubility (mg/mL)
Oils
Labrafac® Lipophile WL1349	9.36±0.01
Labrafil® M1944	13.45±0.02
Ethyl oleate	8.82±0.02
Surfactants
Cremophor® EL	45.32±0.04
Tween-80	36.21±0.03
Peceol®	20.12±0.01
Cosurfactants
PEG-400	43.79±0.06
Glycerin	68.36±0.20

Notes: Data are expressed as the mean ± standard deviation (n=3). Labrafac® Lipophile, Labrafil® and Peceol® (Gattefosse, Saint-Priest Cedex, France). Tween-80 (Shenyu Pharmaceutical and Chemical Co, Ltd, Shanghai, People’s Republic of China). PEG-400 (Tiantai Fine Chemical Co, Ltd, Tianjin, People’s Republic of China). Glycerin (Bodi Chemical Co, Ltd, Tianjin, People’s Republic of China). Cremophor® EL (BASF, Ludwigshafen, Germany).

Table 3 Turbidity of different mixtures of oil and surfactant dispersed in water at 25°C

	Turbidity
	Labrafil® M1944	Labrafac® Lipophile WL1349
Cremophor® EL	0.836	0.725
Tween-80	0.609	0.714

Notes: Labrafac® Lipophile and Labrafil® (Gattefosse, Saint-Priest Cedex, France). Tween-80 (Shenyu Pharmaceutical and Chemical Co, Ltd, Shanghai, People’s Republic of China). Cremophor® EL (BASF, Ludwigshafen, Germany).

Figure 2 Ternary phase diagrams of different selected systems dispersed in water at 25°C. The shadow area represents the oil in water (o/w) nanoemulsion region.

Notes: Labrafac® Lipophile and Labrafil® (Gattefosse, Saint-Priest Cedex, France). Tween-80 (Shenyu Pharmaceutical and Chemical Co, Ltd, Shanghai, People’s Republic of China). Cremophor® EL (BASF, Ludwigshafen, Germany). Glycerin (Bodi Chemical Co, Ltd, Tianjin, People’s Republic of China).

Figure 3 Transmission electron micrograph of 25-OCH₃-PPD-loaded self-microemulsifying drug-delivery system.

Table 4 Main pharmacokinetic parameters of 25-OCH₃-PPD after oral administration of 25-OCH₃-PPD-loaded SMEDDS and suspension at dose of 5 mg/kg to rats

Parameter	SMEDDS	Suspension
Cmax (ng/mL)	352.40±223.61	80.93±43.58*
Tmax (hours)	5.75±2.75	2.75±1.13*
t1/2 (hours)	8.71±2.72	4.71±2.60*
AUC0–t (ng/hour/mL)	2,788.68±1,668.64	372.38±265.57*
AUC0–∞ (ng/hour/mL)	6,152.09±2,635.65	630.27±375.32*

Notes:

* P<0.05 versus 25-OCH₃-PPD SMEDDS by Student’s t-test. Each value represents the mean ± standard deviation (n=6).

Abbreviations: SMEDDS, self-microemulsifying drug-delivery system; AUC, area under the curve; C_max, peak plasma concentration; T_max, time taken to reach peak plasma concentration; t_1/2, elimination half-life.

Table 5 Main pharmacokinetic parameters of 25-OH-PPD after oral administration of 25-OCH₃-PPD-loaded SMEDDS and suspension at dose of 5 mg/kg to rats

Parameter	SMEDDS	Suspension
Cmax (ng/mL)	841.33±240.64	313.10±279.56*
Tmax (hours)	8.41±3.67	3.08±1.07*
t1/2 (hours)	8.77±7.61	4.90±1.79
AUC0–t (ng/hour/mL)	12,569.17±3,999.48	2,792.24±2,663.89*
AUC0–∞ (ng/hour/mL)	19,501.06±10,913.65	3,009.08±2,893.44*

Notes:

* P<0.05 versus 25-OCH₃-PPD SMEDDS by Student’s t-test. Each value represents the mean ± standard deviation (n=6).

Abbreviations: SMEDDS, self-microemulsifying drug-delivery system; AUC, area under the curve; C_max, peak plasma concentration; T_max, time taken to reach peak plasma concentration; t_1/2, elimination half-life.

Figure 4 Mean rats plasma concentration-time profiles of 25-OCH₃-PPD after oral administration of 25-OCH₃-PPD-loaded SMEDDS and suspension to rats at dose of 5 mg/kg (each point represents the mean ± standard deviation, n=6).

Abbreviation: SMEDDS, self-microemulsifying drug delivery system.

Figure 5 Mean rats plasma concentration-time profiles of metabolite 25-OH-PPD after oral administration of 25-OCH₃-PPD-loaded SMEDDS and suspension to rats at dose of 5 mg/kg (each point represents the mean ± standard deviation, n=6).

Abbreviation: SMEDDS, self-microemulsifying drug delivery system.