The advent of combinatorial chemistry and high throughput screening as the primary technologies for drug discovery has resulted in the generation of a preponderance of potential drug candidates, which do not possess favorable "drug-like" biopharma-ceutical properties. Specifically, these candidate compounds are highly lipophilic (Log P > 5) and possess very poor solubility (<10mg/mL) in physiological fluids, resulting in poor and highly variable absorption, after oral administration, that is often strongly influenced by the presence of food in the gastrointestinal (GI) tract (1). In many instances, the GI absorption of these challenging compounds can be significantly improved through the use of lipid-based formulations (2,3).
In addition to improving and normalizing the absorption of poorly water-soluble drugs, lipid based formulations can be used to address other formulation issues, including stabilization of oxygen and moisture sensitive compounds (4), improving content uniformity of the dosage form (5) and allowing for controlled drug release (6,7). Despite the promise that lipid formulation technology holds for addressing challenging formulation issues, research and development activities in this area have been limited and only a few marketed products employ lipids as primary excipients.
Physiological factors that can influence the rate and extent of drug absorption from a lipid-based formulation include GI lipid digestion (8-10) and the emulsion droplet size formed upon mixing with the GI fluids (2,11,12). From a manufacturing perspective, the solubility of the drug substance in the lipid vehicle controls the drug loading of the formulation, whereas the stability of the drug can be influenced by the excipient peroxide and acid values and the degree of lipid fatty acid saturation and hygroscopicity. During manufacturing of semi-solid lipid dispersion formulations, the rate of shear applied during mixing should be carefully evaluated and monitored (4) and the rate of cooling of the formulation must be controlled as it can influence the formulation final viscosity, content uniformity, dissolution rate, and efficiency of the encapsulation process.
Was this article helpful?