This document discusses self-microemulsifying drug delivery systems (SMEDDS), which are mixtures of oils, surfactants, and sometimes co-surfactants that form fine oil droplets upon mixing with water. SMEDDS can improve the solubility and absorption of poorly water-soluble drugs. When taken orally, SMEDDS form microemulsions in the gastrointestinal tract that solubilize drugs and allow absorption via lymphatic pathways. The document outlines the components, advantages, and mechanisms of SMEDDS for enhancing oral bioavailability of lipophilic drugs.

1. SELF MICRO EMULSIFYING DRUG DELIVERY
SYSTEM (SMEDDS)
Megha
Assistant Professor

2. BACKGROUND
The concept was first introduced by hoar and Schulman in 1940s who
generated a clear single phase solution by titrating a milky emulsion with
hexanol.
Schulman and co-worker in 1959 subsequently coined the term
microemulsion.

3. INTRODUCTION
• Solubility of orally administered drug is major challenge of
pharmaceutical industry as nearly 35-40% of newly launched drugs
possess low aqueous solubility which leads to their poor dissolution
and low bioavailability, resulting in high intra and inter subject
variability & lack of dose proportionality. In recent years, much
attention has been focused on oral dosage forms using a self micro
emulsifying drug delivery system(SMEDDS) for the purpose of
improving the solubility and absorption of poorly water soluble
drugs.
• When SMEDDS formulation is released in the lumen of the
gastrointestinal tract, they come in contact with GI fluid and form a
fine emulsion (micro) So called as self-emulsification which further
leads to solubilization of drug that can subsequently be absorbed by
lymphatic pathways, bypassing the hepatic first-pass effect. This
enhancing bioavailability properties .

4. Process of self emulsifications
SMEDDS

5. DEFINITION
SMEDDS are defined as isotropic mixtures of natural
or synthetic oils, solid and liquid surfactants”
▶ SMEDDS consists of a mixture of drugs, oils, surfactants and co-
surfactants. Gentle mixing of these ingredients in aqueous media
generates micro emulsions with a droplet size in a range of 10-100
nm.
▶ Resultant small droplet size from SMEDDS provides a large
interfacial surface area for drug release and absorption and the
specific components of SMEDDS promote the intestinal lymphatic
transport of drugs. Thus oral absorption of certain drugs has been
enhanced by SMEDDS
▶ The BCS Class II drugs has poor solubility e.g. Diclofenac,
verapamil and it leads to marked improvement in absorption of Class
IV drugs which have both dissolution and permeability rate limited
absorption.

6. FEATURE SEDDS SMEDDS
COMPOSITION Oil+ Surfactant+ Drug Oil + surfactant+ Co-surfactant+
Drug
SIZE OF DROPLET 200 nm – 5µm less than 200nm
APPEARANCE Turbid in Nature Transparent in Nature
THERMODYNAMICAL
LY
Not stable Stable
PHASE DIAGRAM Ternary phase Pseudo ternary phase
CON. OF OIL 40-80% less than 20% as compared to
SEDDS

7. MICROEMULSION EMULSION

8. ADAVANTAGE
1. Fine oil droplets of SMEDDS would pass rapidly facilitating
wide distribution of the drug throughout the stomach and
promote wide distribution of the drug throughout the GI tract.
2. SMEDDS are physically stable formulations.
3. As compared with oily solutions, they provide a large interfacial
area for partitioning of the drug between oil and water.
4. Potential advantages of these systems include enhanced oral
bioavailability, more consistent temporal profiles of drug
absorption.
5. Ease of manufacture and scale- up.

9. DISADVANTAGE
1. Dissolution of these formulations potentially are dependent on
digestion prior to release of the drug.
2. chemical instabilities of drugs and high surfactant concentrations
in formulations (approximately 30-60%) which irritate GIT.
3. Volatile co-solvents in the conventional SMEDDS formulations
are known to migrate into the shells of soft or hard gelatin
capsules, resulting in the precipitation of the lipophilic drugs
4. High production costs.
5. drug incompatibility.
6. Drug leakage. So it may allow less drug loading.

10. COMPOSITION
OF SMEDDS
EXCIPIENTS
OIL SURFACTANT
CO-
SURF
ACT
ANT
API
DRUG
BELONG TO
BCS CLASS 2

11. 1) Active pharmaceutical ingredient (API
Active Pharmaceutical Ingredient (API): As, SMEDDS are used to
increase the solubility of poor water-soluble drugs, BCS class II
drugs are preferred e.g. itraconazole, nifedipine, vitamin E,
simvastatin, danazol, ketoconazole, naproxen, carbamazepine .

12. 2) Oils
Oils can solubilize the required dose of the lipophilic drug and facilitate
self emulsification and also they can increase the fraction of lipophilic
drug transported via the intestinal lymphatic system, thereby increasing
absorption from the GI tract depending on the molecular nature of the
triglyceride.
oils drugs Market products
Corn oil Valproic acid Depakene capsule
Sesame oil Dronabinol Marinol soft
gelatin capsule
Soya bean oil Isotretinoin Accutane soft
gelatin capsule
Peanut oil Progesterone Prometrium soft
gelatin capsule

13. 3) Surfactant
1. Surfactants are compounds that lower the surface tension (or interfacial
tension) between two liquids, between a gas and a liquid, or between a
liquid and a solid.
2. improve the bioavailability by various mechanisms including: improved
drug dissolution, increased intestinal epithelial permeability, increased
tight junction permeability and decreased/inhibited p-glycoprotein drug
efflux.
SURFACTANTS DRUGS MARKETED
PRODUCT
SPAN 80,TWEEN 80 Cyclosporine Gengraf soft gelatin
capsule
TWEEN 20 Bexarotene Targretin Hard gelatin
Capsule
CREMOPHOR RH 40 Carmustine BCNU self-emulsifying
implant

14. 4) Co-surfactants
The production of an optimum SMEDDS requires relatively high
concentrations (generally more than 30% w/w) of surfactants but it
causes GI irritation. So co surfactant is used to reduce concentration
of surfactant. Role of the co surfactant together with the surfactant is
to lower the interfacial tension .
EXAMPLE:-
▶ Ethanol
▶ Glycerin
▶ PEG

15. MECHANISM
The free energy of the emulsion can be described by equation:
Δ𝐺 = ∑𝑁Π𝑟2𝜎
Δ𝐺 is the free energy,
𝑁 is the number of droplets,
𝑟 is the radius of droplets, and
𝜎 is the interfacial energy.
In SMEDDS, emulsion formation occurs instantaneously because
the free energy of the system is very low and sometimes negative
due to the presence of flexible interface.

16. • From this equation, it is evident that the lower the Inter facial
energy the lower the free energy.
• Self-emulsification occurs when the energy involvement in the
dispersion is greater than the energy required for the formation of
droplets .
• The free energy of conventional emulsion is very high as high
energy is required to form new surface between two immiscible
phases like oil and water.
• Due to high free energy, the emulsion may not be stable and the
two phases tend to separate.
• But in case of SMEDDS, emulsion formation occurs
instantaneously because the free energy of the system is very low
and sometimes negative due to the presence of flexible interface.