Complex Interplay Between Solubilization, Digestion, Supersaturation and Absorption of Poorly Soluble Drugs with Lipid-Based Formulations

Lipid-based formulations (LBFs) can be effective oral drug delivery systems for poorly water-soluble chemical entities, provided they are designed with careful selection of the excipients, based on their role in the delivery system and in relation to the drug properties [1]. LBFs comprise four types of formulations (type I, II, III A and B, IV) containing mixture of oils, surfactants and hydrophilic cosolvents, some of which are able to self-emulsify in contact with the gastrointestinal medium [2]. Key considerations in the selection step must be the series of mechanisms underpinning oral bioavailability enhancement. The primary factor leading to increased bioavailability by LBFs is the administration of the drug in a pre-dissolved state thus avoiding the solid-to-liquid phase transition process. Moreover, the interactions between the LBF and the endogenous lipids such as bile salts, phospholipids and dietary lipids will help maintain the drug in solution within colloidal structures [3]. The fate of a drug formulated in a LBF is hence dependent on the ability of the formulation components to keep the drug in solution during the initial dispersion and/or digestion processes [4]. These systems should therefore be formulated by the wise selection of excipients based on their intended function: some excipients are needed to dissolve the drug within the dosage form; some to promote self-emulsification, and others to generate the metabolites that maintain drug solubility in the gastro-intestinal colloidal phases. Standardized in vitro tests of dispersion and digestion are now available to help predict the in vivo performance of LBFs [5]. The in vitro digestion test enables the evaluation of the fraction of drug in micellar solution and in supersaturation - the latter known to enhance drug absorption [6].