Lipid formulations for oral administration of drugs: non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems

Abstract

‘Lipid’ formulations for oral administration of drugs generally consist of a drug dissolved in a blend of two or more excipients, which may be triglyceride oils, partial glycerides, surfactants or co-surfactants. The primary mechanism of action which leads to improved bioavailability is usually avoidance, or partial avoidance, of the slow dissolution process which limits the bioavailability of hydrophobic drugs from solid dosage forms. Ideally the formulation allows the drug to remain in a dissolved state throughout its transit through the gastrointestinal tract. The availability of the drug for absorption can be enhanced by presentation of the drug as a solubilizate within a colloidal dispersion. This objective can be achieved by formulation of the drug in a self-emulsifying system or alternatively by taking advantage of the natural process of triglyceride digestion. In practice ‘lipid’ formulations range from pure oils, at one extreme, to blends which contain a substantial proportion of hydrophilic surfactants or cosolvents. Knowledge of the efficiency of emulsification of these formulations, the nature of the colloidal system formed by dispersion, their susceptibility to digestion, and the subsequent fate of the drug is desirable for formulation. Yet the literature on this subject is limited, so this article represents part review and part commentary on current status of lipid formulations. A simple classification system for lipid formulations, based on the polarity of the blend and reviewed here, will help comparison of data between laboratories. Priorities for future work are discussed. More data is needed on the solubility of drugs in various types of formulations, and in particular, on the relationship between the physical chemistry of the drug and its fate, subsequent to dilution and digestion of the formulation in the lumen of the gastrointestinal tract. The mechanisms of action and practical uses of each type of lipid formulation are discussed.