title: Synergistic role of solid lipid and porous silica in improving the oral delivery of weakly basic poorly water soluble drugs.
abstract: Oral absorption of weakly basic drugs (e.g. cinnarizine (CIN)) is limited by their pH dependent precipitation in intestinal conditions. To overcome this challenge, a novel drug delivery system composed of solid lipid and porous silica, namely silica encapsulated solid lipid (SESL) particles, was developed via hot homogenization of melted lipid dispersion, followed by ultra-sonication of the silica stabilized homogenized melted lipid dispersion. Scanning electron microscope (SEM) images of the SESL formulation revealed non-spherical and aggregated hybrid particles, with rough exterior and structured nanoparticles visible on the surface. A 1.5, 2.2 and 7-fold improvement in the dissolution of CIN was observed for the SESL particles, under simulated intestinal non-digesting conditions, in comparison to the drug loaded in solid lipid (CIN-SL) matrix, drug loaded in porous silica (CIN-PS) and pure drug powder. Under simulated intestinal digestive condition, significant improvement in the drug solubilization was reported for the SESL formulation in compared to the individual drug loaded systems i.e. CIN-PS and CIN-SL. Thereby, silica encapsulated solid lipid system provides a promising oral delivery approach for poorly water soluble weakly basic drugs.
authors: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
authors: Rokhsana
authors: R
authors: Yasmin
authors: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
authors: Shasha
authors: S
authors: Rao
authors: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
authors: Kristen
authors: K
authors: Bremmell
authors: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia. Electronic address: Clive.Prestidge@unisa.edu.au.
authors: Clive
authors: C
authors: Prestidge
mesh_terms: D000284:Administration, Oral; D002936:Cinnarizine / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004357:Drug Synergism; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D016062:Porosity; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D012995:Solubility; D014867:Water / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D008055:Lipids; D014867:Water; D002936:Cinnarizine; D012822:Silicon Dioxide
keywords: Oral delivery; Poorly water soluble drugs; Porous silica; Solid lipid; Solubilization