Self-emulsifying drug delivery systems as a tool to improve solubility and bioavailability of resveratrol

Figures & data

Table 1 Composition and visual assessment of different self-emulsifying drug delivery system formulations

Formula	Components (mg)			Visual observation
	Oil	Tween 80	Propylene glycol
F1	100	450	450	Good
F2	100	600	300	Good
F3	100	675	225	Good
F4	100	720	180	Good
F5	100	300	600	Good
F6	100	225	675	Good
F7	100	180	720	Good
F8	150	425	425	Good
F9	150	566.7	283.3	Good
F10	150	637.5	215.5	Good
F11	150	680	170	Good
F12	150	283.3	566.7	Good
F13	150	215.5	637.5	Good
F14	150	170	680	Good
F15	200	400	400	Bad
F16	200	533.3	266.7	Bad
F17	200	600	200	Good
F18	200	640	160	Good
F19	200	266.7	533.3	Good
F20	200	200	600	Good
F21	200	160	640	Good
F22	300	350	350	Bad
F23	300	466.7	233.3	Bad
F24	300	525	175	Bad
F25	300	560	140	Good
F26	300	233.3	466.7	Good
F27	300	175	525	Good
F28	300	140	560	Good

Table 2 Solubility profile of resveratrol at different oils, surfactants, and cosurfactants

Vehicle	Solubility (mg/mL)
Oleic acid	0.326±0.075
Olive oil	5.228±0.23
Soybean oil	4.004±0.63
Almond oil	4.066±0.54
Tween 80	9.809±0.67
Tween 20	8.084±0.58
Propylene glycol	9.228±0.28
PEG 400	8.111±0.83
n-Butanol	8.084±0.37

Note: Data are presented as mean ± standard deviation.

Figure 1 Ternary phase diagram of mixture consisting of olive oil, propylene glycol, and Tween 80.

Table 3 Emulsification time, mean droplet size, zeta potential, percentage drug released after 5 minutes (Q5) and 60 minutes (Q60), and percentage dissolution efficiency (%DE) of various formulations of self-emulsifying drug delivery system

Formula	Emulsification time (s)	Mean droplet size (nm)	Zeta potential (mV)	Q5	Q60	%DE
F3	20±1.3	440±9.9	−9.73±0.16	76±1.6	88.0±2.1	86.5
F4	17±0.5	285±2.6	−13.7±0.2	90±2.4	95.2±1.1	89.6
F5	20±1.1	404±5.6	−8.76±0.12	75±2.1	90.7±2.0	76.7
F6	20±0.9	420±4.9	−5.7±0.1	80±1.7	88.7±1.8	80.7
F7	29±1.3	459±5.5	−5.45±0.3	78±2.3	88.2±0.9	81.0
F8	34±1.7	477±1.07	−5.18±0.2	87±2.0	95.3±0.8	90.1
F9	17±1.5	471±3.6	−6.84±0.1	83±1.9	96.0±1.7	86.9
F19*	27±0.8	336±11.6	−15.4±0.6	94±1.1	100±0.6	95.5
F20	23±0.6	380±5.6	−11.9±0.2	79±2.2	95.5±2.1	88.1
F21	32±1.3	423±4.4	−8.6±0.03	78±0.9	94.0±1.7	85.4
F26	75±3.2	823±3.2	−3.7±0.5	77±3.1	85.0±2.8	82.5
F27	99±2.7	775±6.2	−2.2±0.4	73±2.5	78.7±2.3	73.5
Pure drug	NA	NA	NA	19±1.3	55±2.2	42.5

Notes: Data are presented as mean ± standard deviation.

* F19 is the optimal formula that was selected for in vivo studies.

Abbreviation: NA, not applied.

Figure 2 Dissolution profiles of resveratrol from different self-emulsifying drug delivery system formulations prepared using different oil ratios of 10% (A), 15% (B), 20% (C), and 30% (D).

Table 4 The effect of orally administered optimized resveratrol SEDDS (F19) compared with unprocessed resveratrol on body weight and serum glucose level in streptozotocin-induced diabetes mellitus in male albino rats

Group	Body weight (g)		Serum glucose level (mg/dL)
	Before treatment	After 4 weeks treatment	At the onset	At the end of experiment
N	195.12±3.9	219.9±8.81	95.5±3.6	106.3±3.4
DM	189.6±7.1	129.6±4.01*	296.8±9.1*	449.8±7.9*
CRV10	194.0±5.6	168.25±2.8*,**	282.8±7.6*	196.4±6.74*,**
FRV10	180.8±3.92	185.6±4.98*,**,***	266.35±5*,**	179.7±3.92*,**,***
CRV20	192.8±8.9	188.5±13.4**,***	272.3±4.4*,**	170.5±3.43*,**,***
FRV20	196.6±7.01	190.2±4.8**,***	267.6.±4.8*	172.3±4.15*,**,***

Notes: Values were expressed as mean ± standard error (n=10 per group). P-value is <0.05;

* significant difference vs N group;

** significant difference vs DM group; and

*** significant vs CRV10.

Abbreviations: N, nondiabetic control; DM, streptozotocin-induced diabetes; CRV10, DM treated with unprocessed resveratrol (10 mg/kg/day); FRV10, DM treated with optimal formula of resveratrol SEDDS (F19) (10 mg/kg/day); CRV20, DM treated with unprocessed resveratrol (20 mg/kg/day); FRV20, DM treated with optimal formula of resveratrol SEDDS (F19) (20 mg/kg/day); SEDDS, self-emulsifying drug delivery system.

Figure 3 Effect of orally administered optimized resveratrol SEDDS (F19) compared with unprocessed resveratrol on serum lipid levels in streptozotocin-induced diabetes mellitus in male albino rats.

Notes: Values were expressed as mean ± standard error (n=10 per group). P-value is <0.05; *significant difference vs N group.
Abbreviations: N, nondiabetic control; DM, streptozotocin-induced diabetes; CRV10, DM treated with unprocessed resveratrol (10 mg/kg/day); FRV10, DM treated with optimal formula of resveratrol SEDDS (F19) (10 mg/kg/day); CRV20, DM treated with unprocessed resveratrol (20 mg/kg/day); FRV20, DM treated with optimal formula of resveratrol SEDDS (F19) (20 mg/kg/day); SEDDS, self-emulsifying drug delivery system; TC, total cholesterol; LDL-C, low density lipoprotein-cholesterol; HDL-C, high density lipoprotein-cholesterol; TG, triglycerides.