SEDDSs and SMEDDSs are easily manufactured and physically stable isotropic mixtures of oil, surfactant, cosurfactant and solubilized drug substance that are suitable for oral delivery in soft and hard gelatin [(or hard hydroxypropyl methylcellu-lose (HPMC)] capsules. These formulations that rapidly and spontaneously form fine oil in water emulsions or microemulsions upon dilution in water (8), owe their self-emulsifying properties to a negative or low free energy requirement for emulsion formation (9). Thus, self-emulsifying formulations are readily dispersed in the GI tract, where the motility of the stomach and small intestine provides the agitation necessary for emulsification (10). Self-emulsifying properties are conferred upon a formulation by proper selection of the lipid/surfactant pair as well as the optimum ratio concentrations of lipid and surfactant (10-13). In addition, the use of surfactant blends to achieve the hydrophilic-lipophilic balance (HLB) value required for emul-sification has often been proven to provide superior self-emulsifying properties relative to the use of a single surfactant possessing the desired HLB (9,14).
One or more cosolvents are often added to the formulation to assist in sol-ubilizing high concentrations of the drug (5). SEDDS produce opaque, white emulsions with lipid droplet sizes of approximately 100 nm, while SMEDDS form transparent microemulsions with a droplet size of less than 50 nm (8).
The small lipid droplet size and associated greater lipid surface area produced by SEDDS and particularly, SMEDDS formulations facilitates lipid digestion, resulting in more rapid incorporation of the drug into bile salt mixed micelles. The end result is an increase in the degree and uniformity of drug absorption relative to that associated with simple lipid solutions of drug (3). In addition, there is evidence suggesting that the lipid droplets formed by self-emulsifying formulations may facilitate drug absorption directly, independent of the bile salt mixed micelle transport system (15). The improved drug absorption provided by self-emulsifying formulations is contingent upon the maintenance of the drug in the solubilized state until it can be absorbed from the GIT (4). In instances where the lipid vehicle hydrolysis rate exceeds that of drug absorption, lumenal precipitation can occur resulting in suboptimal and more variable drug absorption. This situation was encountered with tributyrin formulations of the poorly soluble antineoplastic drug, penclomedine, which resulted in substantially lower drug absorption as compared to solution formulations of the drug in long chain fatty acids (16). In this instance, the facile GI dispersion and rapid hydrolysis of the more polar tributyrin led to precipitation of penclomedine in the intestinal lumen before it could be absorbed.
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