Controversies with self-emulsifying drug delivery system from pharmacokinetic point of view

Figures & data

Figure 1. Different components of self-emulsifying drug delivery system.

Figure 2. Miceller solubilization of hydrophobic drug in the duodenum.

Figure 3. Mechanism of lymphatic transport from intestine.

Table 1. Terminology used for SEDDS with respect to droplet size.

Drug	Inactive components	Droplet size (nm)	Terminology used (SEDDS/SNEDDS/SMEDDS)
Fenofibrate	Myritol 318 (MCT), TPGS, Tween 80/Tween 20	NR	SMEDDS (Fei et al., 2013)
Finasteride	Labrafac cc (Caprylic/Capric Triglyceridel),Tween 80, Labrasol (caprylocaproyl macrogol-8-glyceride)	22.01–165.7	SMEDDS (Fagir et al., 2015)
Halofantrine	Maisine 35-1 (LC mono-, di-, and triglycerides), Cremophore RH40	33–45	SNEDDS (Thomas et al., 2012)
Berberine HCl	Ethyl linoleate and oleic acid (2:1), Tween-80, Glycerol	23.07	SMEDDS (Zhu et al., 2013)
Andrographolide	Capryol 90, Cremophor RH 40, Labraso	23.4 ± 0.2	SMEDDS (Sermkaew et al., 2013)
Cinnarizine	Sesame oil, Cremophore RH40 and oleic acid, Brij 97	28.1 ± 0.96	SNEDDS (Christiansen et al., 2014)
Silybin	Labrafac CC, Cremophore RH40, Transcutol	49.6	SEDDS (Wei et al., 2012)
Vinpocetine	Labrafac & oleic acid, Cremophor EL Transcutol P	<50	SMEDDS (Chen et al., 2008)
Leuprorelin	Capmul MCM (mono/diglycerides of caprylic acid), Captex (capryl triglyceride), Cremophor EL, propylene glycol	50.1	SMEDDS (Hintzen et al., 2014)
Carotenoid lutein	Phosal 53 (Phosphatidyl choline), labrasol, transcutol P	88.12 ± 3.56	SNEDDS (Shanmugam et al., 2011)
Flubiprofen	Labrafil M 1944 CS, Labrasol, Transcutol P	101 ± 4	SNEDDS (Kang et al., 2012)
Diclofenac Sodium	NR	137	SNEDDS (Kumar et al., 2015)
Darunavir	Capmul MCM C8, tween 80, transcutol P	144 ± 2.3	SNEDDS (Inugala et al., 2015)

MCT: Medium chain triglyceride; TPGS: D-alpha-tocopheryl polyethylene glycol 1000 succinate; NR: Not reported.

Function of components: Myritol, Sesaem oil, Labrafac CC, Maisine, Capryol, Labrafil M1944CS, Capmul MCM, Ethyl linoleate, Oleic acid, Capmul MCM, Phosal 53 are used as lipid/oil component. Cremophore RH & EL, Labrasol, Tween 80 and Tween 20 are used as surfactant. Brij 97, transcutol P, propylene glycol are used as co-surfactant.

Figure 4. In vitro lipolysis model for SEDDS.

Figure 5. In situ single pass intestinal permeation (SPIP) model.

Table 2. Comparative pharmacokinetic parameters of liquid and solid SMEDDS/SNEDDS.

Drug	Solid form	Ingredient used to convert liquid into solid dosage form	Pharmacokinetic parameters after oral administration	Observation
Lutein (Shanmugam et al., 2011)	Spray-dried powder (solid SNEDDS)	Colloidal silica	AUC0–48: equal; Cmax: 0.85 times; tmax: same (compared to liquid SNEDDS)	i. In vivo parameters are same in solid form and liquid form of SNEDDS.ii. Both liquid and solid SNEDDS possessed ∼2.8 time higher relative oral bioavailability compared to commercial product.
Isradipine (Ramasahayam et al., 2015)	Powder (solid SNEDDS)	Magnesium aluminometasilicate	AUC0–α: 2.5 times; Cmax: 2.9 times; tmax: 0.49 times (compared to pure drug solution)	i. No in vivo comparison with liquid SNEDDS was done.
Lornoxicam (Li et al., 2015)	Lyophilized powder (solid SMEDDS)	Sucrose	AUC0–α: 1.5 times; Cmax: 1.74 times; tmax: 0.72 times (compared to commercial tablet)	i. No in vivo comparison with liquid SNEDDS was done.
Docetaxel (Quan et al., 2013)	Spray-dried powder (solid SNEDDS)	Amorphous silica	AUC: 4.8 times; Cmax: 8.1 times; tmax: 0.87 times (compared to pure drug solution)	i. No in vivo comparison with liquid SNEDDS was done.ii. Absolute bioavailability was reported as 12.6% for solid SNEDDS where as 2.6% for oral solution.
Flubiprofen (Kim et al., 2012)	Spray-dried powder (solid SMEDDS) filled in hard gelatin capsule	Gelatin	AUC: 3.6 times; Cmax: 3.7 times; tmax: 1.2 times (compared to commercial product)	i. No in vivo comparison with liquid SMEDDS was done.ii. tmax is little bit longer than commercial product
Clopidogrel (Kim et al., 2014)	Spray-dried powder (solid SMEDDS)	Silicon di oxide	AUC: 0.66 times, Cmax: 0.57 times, tmax: 1.45 times (compared to solid dispersed formulation)	i. No in vivo comparison with liquid SMEDDS was done.ii. Solid dispersed formulation showed better in vivo results than solid SMEDDS.
Fenofibrate (Kim et al., 2013)	Spray-dried powder	Dextran	AUC: 2.2 times and Cmax: 4.0 times; tmax: approximately half (compared to normal powder)	No in vivo comparison with liquid SMEDDS was done.
Dutasteride (Kim et al., 2015)	Powder (solid SMEDDS)	Aerosil 200 along with a hydrophilic polymer (soluplus),	AUC0–36: 1.1 times, Cmax: 1.1 times; tmax: half (compared to commercial product)	No in vivo comparison with liquid SMEDDS was done.ii. Pharmacokinetic parameters were not significantly improved compared to commercial product.

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