Solid-state lipid-based formulations offer great potential for the improved oral delivery of poorly water-soluble drugs. This study investigates the use of the high-surface-area clay materials, montmorillonite and laponite, as solid carriers for lipid-based formulations. The unique cation-exchange properties of clay platelets were exploited to preload the ionizable hydrophobic compound, blonanserin, prior to encapsulating a drug-loaded lipid solution. Thus, solid-state lipid-based formulations with dual-loading capabilities were developed and studied. These formulations were compared with simple clay-based lipid formulations, where blonanserin was loaded in the lipid phase only. The drug release behavior of all clay-based formulations was assessed during in vitro dissolution studies under simulated gastric conditions and in vitro fasting intestinal lipolysis studies. Montmorillonite- and laponite-based lipid formulations significantly reduced blonanserin solubilization relative to a control lipid solution and silica–lipid hybrid particles, owing to incomplete drug release from the clay cation-exchange sites. This phenomenon was replicated during in vivo pharmacokinetic studies, whereby the bioavailability of simple clay-based lipid formulations was decreased relative to controls. Importantly, the solid-state dual-loaded montmorillonite-based lipid formulation provided an optimal pharmacokinetic performance, achieving the same degree of bioavailability enhancement as the control lipid solution. These findings indicate the potential of solid-state dual-loaded clay-based lipid formulations for increasing drug loading levels and enhancing the oral absorption of poorly soluble weak base compounds.
- Cation exchange
- lipid-based formulation
- Poorly water-soluble drug
Dening, T. J., Thomas, N., Rao, S., van Looveren, C., Cuyckens, F., Holm, R., & Prestidge, C. A. (2018). Montmorillonite and Laponite Clay Materials for the Solidification of Lipid-Based Formulations for the Basic Drug Blonanserin: In Vitro and in Vivo Investigations. Molecular Pharmaceutics, 15(9), 4148–4160. https://doi.org/10.1021/acs.molpharmaceut.8b00555