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.

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 molecules (10).

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 systems.

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 a SEDDS:

• The solubility of the drug in different oil, surfactants and cosolvents.
• 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 the equation:

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, 17).

Turbidity Measurement. This is to identify efficient self-emulsification by establishing whether the dispersion reaches equilibrium rapidly and in a reproducible time.