Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid Naringenin: design, characterization, in vitro and in vivo evaluation

Figures & data

Table 1. Observation for dispersibility test.

S. No	Grade	Dispersibility and appearance	Time of self-emulsification (min)
1	A	Rapidly forming nanoemulsion, having a clear or bluish appearance	<1
2	B	Rapidly forming, slightly less clear nanoemulsion, having a bluish white appearance	<2
3	C	Fine milky emulsion	<2
4	D	Dull grayish white emulsion having slightly oily appearance that is slow to emulsify	>3
5	E	Formulation exhibiting either poor or minimal emulsification with large oil globules present on the surface	>3

Figure 1. Solubility of NRG in different oils.

Figure 2. Oil solubilized (weight %) by different surfactants.

Figure 3. Ternary phase diagrams indicating o/w nanoemulsion region at different Smix ratios (A) Triacetin, Smix (Tween80 and Transcutol HP) and water (B) Triacetin, Smix (Cremophor EL and Transcutol HP) and water.

Table 2. Thermodynamic stability tests of drug-loaded formulations.

	Components ratio (v/v)				Evaluation
Formulation code	Oil	Surfactant	Co-surfactant	Dilution with water	Cent	F/T	H/C	Inference
T2	20	64	16	A	√	x	√	Failed
T3	20	60	20	A	√	x	x	Failed
T4	20	53	27	A	√	√	√	Passed
T7	25	60	15	A	x	√	x	Failed
T8	25	56	19	A	√	√	√	Passed
T9	25	50	25	A	x	√	x	Failed
T12	25	56	14	A	√	√	x	Failed
T13	30	52.5	17.5	B	√	√	√	Passed
T14	30	47	23	A	√	√	√	Passed
T18	35	49	16	B	x	√	x	Failed
T19	35	42.5	22.5	B	√	√	√	Passed
TC4	20	53	27	A	√	x	x	Failed
TC9	25	50	25	B	x	x	√	Failed
TC14	30	47	23	B	√	√	√	Passed
TC19	35	42.5	22.5	B	√	√	√	Passed

Cent: centrifugation; F/T: Freeze-thaw cycle; H/C: heating–cooling cycle.

Table 3. In vitro characterization of optimized SNEDDS formulations.

Formulation	Emulsification time (s)	Mean Droplet size (nm)	Poly dispersity index	Zeta potential (mV)	% Transmittance
T8	46.76 ± 3.61	36.2 ± 3.63	0.252 ± 0.003	−15.37 ± 3.4	92.31 ± 0.21
T13	72.42 ± 2.42	34.5 ± 2.91	0.433 ± 0.001	−19.67 ± 2.3	90.57 ± 0.43
T14	57.87 ± 2.56	38.2 ± 4.17	0.381 ± 0.002	−23.33 ± 1.9	96.21 ± 0.17
T19	64.69 ± 4.01	42.1 ± 2.47	0.365 ± 0.004	−18.21 ± 3.7	95.31 ± 0.48
TC14	90.67 ± 2.56	136.23 ± 5.36	0.515 ± 0.003	−13.26 ± 2.7	75.31 ± 0.34
TC19	96.34 ± 2.13	153.21 ± 6.23	0.486 ± 0.002	−12.36 ± 2.6	78.13 ± 0.57

Figure 4. Transmission electron microscopic (TEM) image of T14 Formulation.

Figure 5. In vitro drug release in phosphate buffer (pH 6.8).

Figure 6. Drug plasma concentration time profile after oral administration of SNEDDS and NRG suspension.

Table 4. Pharmacokinetics parameters of optimized formulation and NRG.

Formulation	Cmax (ng/ml)	Tmax (h)	AUC0–24 (ngh/ml)	AUC0–∞ (ngh/ml)	T1/2 (h)
Drug	5745.79 ± 78	0.50	33109.82 ± 1920	37347.29 ± 1619	7.98 ± 0.24
SNEDDS T14	28345.48 ± 134	0.25	93237.94 ± 3311	105911.1 ± 2832	7.59 ± 0.23