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LIPIDS
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Introduction
Improving the Performance of Lipid Formulations:
Nanoparticle Layers and Solid Hybrid Particles
Angel Tan, Ph.D. and Clive Prestidge, Ph.D.
Ian Wark Research Institute University of South Australia
Lipid-based drug delivery systems are developed to mimic the food (or post-prandial) effect to address the oral bioavailability challenges of low solubility drugs and vitamins. That is, the molecules are effectively solubilized in the lipophilic microenvironment generated by the presence of fat and their corresponding digested fatty acid products mixed with endogenous micellar
components [1, 2].
The diversity of commercialized lipid excipients (e.g. fatty acids, glycerides, polyoxyethylene glycols derivatives, ethoxylated glycerides and polyalcohol fatty acid esters) has created a large platform for lipid-based formulation design, such as in the forms of emulsions, microemulsions, micelles,
liquid crystalline particles, solid lipid
particles and various self-emulsifying systems [3-7]. Successfully marketed oral lipid-based drug products, currently comprising ≤ 4% of the global pharmaceutical market, are mostly formulated as bulk liquid solutions or liquid-filled gelatin capsules [3]. Clinical translation of novel lipid-based formulations is clearly behind the rate of discovery of pipeline drugs exhibiting poor aqueous solubility, which is predicted to increase from 30% to 70% [3, 8]. Major barriers to attaining full commercial potential for lipid-based formulations are associated with challenges in their physical stability, non-ideal drug encapsulation and unpredictable delivery performance.
Here we report on the application of engineered silica nanoparticle layers and specific nanostructures to integrate several attractive biopharmaceutical functions into lipid colloidal systems. Specifically, hybrid silica-lipid particles with nanoporous interiors have been engineered to optimize encapsulation of drugs in their dissolved form as well as to manipulate enzymatic digestion of lipid-based carriers, hence facilitating improved solubilization and absorption of poorly soluble drugs (Figure 1).
Such specific nanostructures can be fabricated by forming at the droplet interface an adlayer of silica nanoparticles of different size, porosity or chemistry based on their self-assembly from the aqueous bulk, followed by a drying process to remove the aqueous phase (e.g. high heat spray-drying, lyophilization under vacuum, or phase coacervation) [9-11]. The fact that pharmaceutical food effects may be mitigated when drug absorption is optimized towards the maximum is an important clinical implication for such solid hybrid particles. These multifaceted functions principally stem from the nanostructure confinement of lipid colloids, where their specific surface area is
8 | | November/December 2013
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