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LIPIDS
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Figure 1. Schematic depiction of key factors aff ecting the rate of drug dissolution, lipid digestion and relative bioavailability of a
poorly water-soluble drug: crystallinity of drug molecules, droplet size of lipid carriers and nanostructure confi nement.
signifi cantly enhanced and the structured lipid arrangement is ideal for facilitating endogenous formulation processing and absorption. In the following, successful proof-of-concept studies are presented to highlight some key roles of silica nanoparticle coating in improving the performance of lipid-based formulations.
Hybrid Particles Enhancing Solid- state Amorphous Drug Encapsulation
For drugs demonstrating low solubility in both aqueous and oily media, the practicability of orally dosing a lipid-based formulation could be
Figure 2. Drug loading enhancement via lipid solubilization and electrostatic adsorption onto silica-lipid hybrid (SLH)
microparticles for a model low solubility drug, albendazole. Data adapted from [21].
hindered by the large volume or amount of excipients required. A majority of lipid-based formulations typically produce ≤ 10% of drug loading levels [12]. Currently marketed oral lipid-based products have been reported to contain up to 5g or 20mL of lipid excipients in capsule dosage forms or solution products, respectively [3]. Some of these products have limited shelf-life at room temperature. Colloidal silica particles, being a chemically inert and biocompatible inorganic solid carrier, have found great application in encapsulating lipid-based formulations in a dry, powdery form. The advantages of such an encapsulation approach are multi-fold. Firstly, powdered lipid-based formulations confer longer term storage stability and potentially enhance chemical protection of volatile and photosensitive drugs [13-17]. Powdered formulations also
Figure 3. Drug release enhancement with silica-lipid hybrid (SLH) formulations for three low solubility drugs: (A) unionized
weak base, celecoxib; (B) pH-dependent weak base, albendazole; and (C) pH-dependent weak acid, indomethacin. Modifi ed from [9], [21] and [24] respectively.
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| November/December 2013
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