Self-nanoemulsifying Drug Delivery Systems: Formulation Insights, Applications and Advances

Abhijit A Date; Neha Desai; Rahul Dixit; Mangal Nagarsenker

Nanomedicine. 2010;5(10)

Overview of Nanoemulsions as a Novel Drug Delivery System

Nanoemulsions offer various advantages for different applications owing to their interesting properties. However, advantages of nanoemulsions pertaining to pharmaceutical research are described below.

Long-term Colloidal Stability

Nanoemulsions can have long-term colloidal stability when fabricated using optimum conditions. Owing to this property, nanoemulsions can be used as drug carriers and can impart long shelf-life to the pharmaceutical product.

Ability to Solubilize Hydrophilic & Hydrophobic Therapeutic Agents

Nanoemulsions have the ability to solubilize hydrophobic as well as hydrophilic drugs in their nanostructure depending on the type of nanoemulsion. The O/W nanoemulsions are used for improving delivery of hydrophobic drugs, whereas W/O nanoemulsions are preferred for incorporating hydrophilic drugs.

Improved Stability of the Therapeutic Agents

Encapsulation of therapeutic agents in nanoemulsions can offer improvements in the chemical and/or enzymatic stability of therapeutic agents, such as 10-methoxy-9-nitrocamptothecin^[8] and cefpodoxime proxetil,^[9] leading to improvement in shelf-life and/or therapeutic efficacy.

Greater Esthetic Appeal & Skin Feel

The low viscosity and transparent (or translucent) nature of nanoemulsions can offer good esthetic appeal, patient compliance and skin feel, and with suitable viscosity modifications, nanoemulsions could be used in patient-friendly 'roll-on'-type formulations, sprays and nanoemulsion gels.

Improved Dermal & Mucosal Transport

Nanoemulsions have demonstrated the ability to enhance the dermal, transdermal and mucosal transport/permeation of various drugs.^[10,11]

Improved Oral Bioavailability

Nanoemulsions have demonstrated tremendous potential in improving oral bioavailability of several therapeutic agents, for example ramipril, ezetimibe, cefpodoxime proxetil and curcumin.^[9,12–14] This aspect is discussed below in greater detail.

Use as a Template to Fabricate Nanoparticulate Systems

The large interfacial area and small droplet size of the nanoemulsions enable them to act as a template for facile fabrication of pharmaceutical nanoparticulate systems, such as solid lipid nanoparticles, polymeric nanoparticles/nanocapsules and drug nanosuspensions.^[15]

Ease of Manufacture & Scale-up

The methods employed for the fabrication of nanoemulsions enable ease of manufacturing and scale-up of nanoemulsions.

Limitations of the Nanoemulsions

Nanoemulsions are not very suitable for controlled drug release applications. Furthermore, the palatability of the nanoemulsion components and compatibility with other excipients could be a major limiting factor in the case of oral drug delivery.

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Cite this: Self-nanoemulsifying Drug Delivery Systems: Formulation Insights, Applications and Advances - Medscape - Dec 01, 2010.

Table 1. Commonly used oily phases.
General class	Examples	Commercial name	Acceptability
Fixed oils	Soybean oil, castor oil	–	P/O/T/Oc/M
MCTs	Triglycerides of capric/caprylic acids	Miglyol 810, 812, Labrafac CC Crodamol GTCC, Captex 300, 355	P/O/T/Oc/M
	Triacetin	Captex 500
Medium-chain mono- and di-glycerides	Mono- and di-glycerides of capric/caprylic acids	Capmul MCM, Imwitor 742, Akoline MCM	O/T
Long-chain mono-glycerides	Glyceryl monooleate	Peceol, Capmul-GMO	O/T
Glyceryl monolinoleate	Maisine-35	O/T
PG fatty acid esters	PG monocaprylate	Capryol 90, Capmul PG-8, Sefsol 218	O/T
	PG monolaurate/dilaurate	Lauroglycol 90, Capmul PG-12, Lauroglycol FCC
	PG dicaprylate/caprate	Miglyol 840, Captex 200
Fatty acid esters	Ethyl oleate	Crodamol EO	P/O/T/Oc/M
	Isopropyl myristate		P/T/Oc/M
	Isopropyl palmitate		P/T/Oc/M
Fatty acids	Oleic acid	Crossential O94	O/T/M
	Caprylic acid		O/T/M
Vitamins	Vitamin E		P/O/T/Oc/M

M: Mucosal; MCT: Medium-chain triglyceride; O: Oral; Oc: Ocular; P: Parenteral; PG: Propylene glycol; T: Topical (dermal).

Table 2. Commonly used surfactants.
General class	Examples	Commercial name	Acceptability
Polysorbates	POE-20-sorbitan monooleate	Tween® 80, Crillet 4	P/O/T/Oc/M
	POE-20-sorbitan monolaurate	Tween 20, Crillet 1	P/O/T/Oc/M
Sorbitan esters	Sorbitan monooleate	Span® 80, Crill 4	P/O/T/Oc/M
	Sorbitan monolaurate	Span 20, Crill 1	P/O/T/Oc/M
	Sorbitan monostearate	Span 60, Crill 3	O/T/M
PEO–PPO–block copolymers	Poloxamer 188	Pluronic®/Lutrol F 68	P/O/T/Oc/M
	Poloxamer 407	Pluronic/Lutrol F 127	O/T/Oc/M
POE castor oil	POE-35-castor oil	Cremphor® EL, Etocas 35 HV	P/O/T/Oc/M
POE hydrogenated castor oil	POE-40-hydrogenated castor oil	Cremophor RH 40, HCO-40, Croduret™ 40 LD	P/O/T/Oc/M
	POE-60-hydrogenated castor oil	Cremophor RH 60, HCO-60	P/O/T/Oc/M
POE-stearate	PEG-660-12-hydroxystearate	Solutol HS 15®	P/O/T/Oc/M
POE-vitamin E	Tocopheryl-PEG 1000-succinate	Vitamin E TPGS	T/O/Oc/M
Sucrose esters	Sucrose laurate		O/T
	Sucrose palmitate		O/T
Polyglycolyzed glycerides	Linoleoyl macrogol glycerides	Labrafil® 2125 CS	O/T
	Oleoyl macrogol glycerides	Labrafil 1944 CS	O/T
	Caprylocaproyl macrogol glyceride	Labrasol®	O/T
	Polyglyceryl oleate	Plurol® oleique CC 497	O/T
	Lauroyl macrogol glycerides	Gelucire® 44/14	O/T
	Stearoyl macrogol glycerides	Gelucire 50/13	O/T
Phospholipids	Soybean lecithin		All routes

M: Mucosal; O: Oral; Oc: Ocular; P: Parenteral; PEG: Polyethylene glycol; POE: Polyoxyethylene; T: Topical (dermal); TPGS: Tocopheryl polyethylene glycol 1000 succinate.

Table 3. List of commonly used solubilizers.
General class	Examples	Acceptability
Short-chain alcohols	Ethanol, benzyl alcohol	P/O/T/Oc/M
Alkane diols and triols	Propylene glycol	P/O/T/Oc/M
	Glycerol	P/O/T/Oc/M
Polyethylene glycols	PEG 400	P/O/T/Oc/M
Glycol ethers	Diethylene glycol monoethyl ether (Transcutol®)	O/T

M: Mucosal; O: Oral; Oc: Ocular; P: Parenteral; PEG: Polyethylene glycol; T: Topical (dermal).

Table 4. Potential of self-nanoemulsifying drug delivery systems in oral drug delivery.
Drug	Theraputic use	Components	In vitro/In vivo observation	Ref.
β-lactamase	A model protein	Hydrogenated lecithin, Cremophor® EL, Transcutol®, Lauroglycol™ FCC	2–3-fold BA increment compared with solution	[90–92]
Biphenyl dimethyl dicarboxylate	Hepatoprotective	Tween® 80, Transcutol, Miglyol® 812	1.7–6-fold improvement in BA	[94]
Coenzyme Q10	Antioxidant	Witepsol® H35, Lauroglycol FCC, Solutol HS 15®	5-fold BA increment compared with powder	[50]
Matrine^†	Natural alkaloid	Cremophor EL, Transcutol, Lauroglycol FCC	Greater BA compared with matrine powder and matrine phospholipid complex	[93]
Probucol	Antihyperlipidemic	Cremophor RH 40, Maisine™ 35, Seasme oil	1.5–3-fold improvement in BA compared with powder	[87]
Zedoary turmeric oil	Essential oil	Transcutol, Ethyl oleate, Tween 80	Improvement in bioavailability	[95]
Oleanolic acid	Hepatoprotective	Cremophor EL, Labrasol®, Transcutol, Sefsol® 218, Cremophor RH 40, PG	2.7-fold BA increment compared with tablets	[96]
Ramipril	Antihypertensive	Tween 80, Sefsol 218, Carbitol	2.29-fold improvement in BA compared with capsules	[12]
Glibenclamide	Antidiabetic	Capmul® MCM, Tween 20, Cremophor RH 40	Greater in vitro dissolution rate	[97]
Lutein	Carotenoid	Labrasol, MCT, PEG 400, Transcutol	Greater in vitro dissolution rate	[64]
Lacidipine	Calcium channel blocker	Labrafil® 1944 CS, Capmul, MCM, Cremophor EL, Tween 80, Transcutol	Greater in vitro dissolution rate	[48]
Retinol acetate	Antioxidant	Soybean oil, Capmul, MCM, Cremophor EL	Improvement in dissolution rate	[98]
Danazol	Antiandrogen	Maisine 35, Cremophor EL, ethanol	Greater in vitro dissolution and no effect of fed and fasted state dissolution media on droplet size	[65]
Halofantrine	Antimalarial
Ibuprofen	Anti-inflammatory	Tween 80, Span 20, Octanediol, IPM, ethanol	Greater in vitro dissolution rate	[54]
Tamoxifen	Anticancer	Cremophor RH 40, PG, Maisine 35, Capryol 90	Improvement in dissolution rate	[67]
Genistein	Natural antioxidant	Labrafac Lipophile™ 1349, Maisine 35, Transcutol, Cremophor EL, Labrasol	100% in vitro drug release in 5 min	[71]
Cyclosporine A	Immunosuppressant	Cremophor EL, Capmul, MCM C8, Orange oil	Improvement in dissolution rate	[68]
Anethole trithione	Chemopreventive	Tween 80, PG, Cremophor RH 40 MCT	Improved stability and in vitro dissolution profile	[63]

^†Matrine-phospholipid complex was incorporated in self-nanoemulsifying drug delivery systems.
BA: Bioavailability; MCT: Medium-chain triglyceride; PG: Propylene glycol.

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Self-nanoemulsifying Drug Delivery Systems: Formulation Insights, Applications and Advances

Overview of Nanoemulsions as a Novel Drug Delivery System

Long-term Colloidal Stability

Ability to Solubilize Hydrophilic & Hydrophobic Therapeutic Agents

Improved Stability of the Therapeutic Agents

Greater Esthetic Appeal & Skin Feel

Improved Dermal & Mucosal Transport

Improved Oral Bioavailability

Use as a Template to Fabricate Nanoparticulate Systems

Ease of Manufacture & Scale-up

Limitations of the Nanoemulsions

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Tables

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References

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