Lyophilized Silica Lipid Hybrid (SLH) Carriers for Poorly Water‐Soluble Drugs: Physicochemical and In Vitro Pharmaceutical Investigations

ABSTRACTLyophilization was investigated to produce a powdery silica–lipid hybrid (SLH) carrier for oral delivery of poorly water‐soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti‐inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray‐dried SLH. 20–50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica‐stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre‐sized particles (<5 μm). The lyophilized SLH produced approximately 1.5‐fold and fivefold increased drug solubilization than the pure drug under nondigesting and digesting conditions, respectively. The feasibility of lyophilization for producing nanostructured SLH formulations with desirable lipid loading and drug solubilization properties for enhanced oral delivery of poorly water‐soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2950–2959, 2014