Composition of SEDDSs
The self-emulsifying process is depends on: (7)
- The nature of the oil–surfactant pair
- The surfactant concentration
- The temperature at which self-emulsification occurs.
Oils. Oils can solubilize the lipophilic drug in a specific
amount. It is the most important excipient because it can
facilitate self-emulsification and increase the fraction of lipophilic
drug transported via the intestinal lymphatic system,
thereby increasing absorption from the GI tract (9).
Long-chain triglyceride and medium-chain triglyceride oils
with different degrees of saturation have been used in the
design of SEDDSs. Modified or hydrolyzed vegetable oils
have contributed widely to the success of SEDDSs owing to
their formulation and physiological advantages (8). Novel
semisynthetic medium-chain triglyceride oils have surfactant
properties and are widely replacing the regular medium-
chain triglyceride (9).
Surfactant. Nonionic surfactants with high hydrophilic–lipophilic
balance (HLB) values are used in formulation of
SEDDSs (e.g., Tween, Labrasol, Labrafac CM 10, Cremophore,
etc.). The usual surfactant strength ranges between
30–60% w/w of the formulation in order to form a stable
SEDDS. Surfactants have a high HLB and hydrophilicity,
which assists the immediate formation of o/w droplets
and/or rapid spreading of the formulation in the aqueous
media. Surfactants are amphiphilic in nature and they can
dissolve or solubilize relatively high amounts of hydrophobic
drug compounds. This can prevent precipitation of the drug
within the GI lumen and for prolonged existence of drug
Cosolvents. Cosolvents like diehylene glycol monoethyle
ether (transcutol), propylene glycol, polyethylene glycol,
polyoxyethylene, propylene carbonate, tetrahydrofurfuryl
alcohol polyethylene glycol ether (Glycofurol), etc., may
help to dissolve large amounts of hydrophilic surfactants
or the hydrophobic drug in the lipid base. These solvents
sometimes play the role of the cosurfactant in the microemulsion
Formulation of SEDDSs
With a large variety of liquid or waxy excipients available,
ranging from oils through biological lipids, hydrophobic and
hydrophilic surfactants, to water-soluble cosolvents, there
are many different combinations that could be formulated
for encapsulation in hard or soft gelatin or mixtures which
disperse to give fine colloidal emulsions (11).
The following should be considered in the formulation of
- The solubility of the drug in different oil, surfactants
- The selection of oil, surfactant and cosolvent based on
the solubility of the drug and the preparation of the
phase diagram (12).
- The preparation of SEDDS formulation by dissolving
the drug in a mix of oil, surfactant and cosolvent.
The addition of a drug to a SEDDS is critical because the
drug interferes with the self-emulsification process to a certain
extent, which leads to a change in the optimal oil–surfactant
ratio. So, the design of an optimal SEDDS requires
preformulation-solubility and phase-diagram studies. In the
case of prolonged SEDDS, formulation is made by adding
the polymer or gelling agent (13).
Mechanism of self-emulsification
According to Reiss, self-emulsification occurs when the
entropy change that favors dispersion is greater than the
energy required to increase the surface area of the dispersion.
The free energy of the conventional emulsion is a direct
function of the energy required to create a new surface
between the oil and water phases and can be described by
Where, DG is the free energy associated with the process
(ignoring the free energy of mixing), N is the number of
droplets of radius r and s represents the interfacial energy.
The two phases of emulsion tend to separate with time to
reduce the interfacial area, and subsequently, the emulsion is
stabilized by emulsifying agents, which form a monolayer of
emulsion droplets, and hence reduces the interfacial energy,
as well as providing a barrier to prevent coalescence (14).
Characterization of SEDDSs
The primary means of self-emulsification assessment is visual
evaluation. The efficiency of self-emulsification could
be estimated by determining the rate of emulsification,
droplet-size distribution and turbidity measurements.
Visual assessment. This may provide important information
about the self-emulsifying and microemulsifying property
of the mixture and about the resulting dispersion (15, 16,
Turbidity Measurement. This is to identify efficient self-emulsification
by establishing whether the dispersion reaches
equilibrium rapidly and in a reproducible time.