Drug Delivery and Translational Research

, Volume 4, Issue 3, pp 212–221

First in man bioavailability and tolerability studies of a silica–lipid hybrid (Lipoceramic) formulation: a Phase I study with ibuprofen

Clinical Trial

DOI: 10.1007/s13346-013-0172-9

Cite this article as:
Tan, A., Eskandar, N.G., Rao, S. et al. Drug Deliv. and Transl. Res. (2014) 4: 212. doi:10.1007/s13346-013-0172-9

Abstract

Clinical trials addressing the viability of lipid and nanoparticle-based solid dosage forms for the oral delivery of poorly water-soluble drugs are limited to date. This Phase I study aimed to assess the comparative tolerability and oral pharmacokinetics of a novel silica nanoparticle–lipid hybrid formulation encapsulating ibuprofen (i.e., Lipoceramic-IBU) with reference to a commercial tablet (i.e., Nurofen®). The test (Lipoceramic-IBU) and reference (Nurofen®) ibuprofen formulations were characterised for physicochemical properties and in vitro solubilisation performance prior to the clinical study. A randomised, double-blinded, one-period single oral dose (20 mg ibuprofen) study was performed in 16 healthy male subjects under fasting conditions. Encapsulation of ibuprofen in a molecularly dispersed form in the Lipoceramic nanostructured silica–lipid matrices was shown to produce superior drug solubilisation in comparison to Nurofen® and the pure drug during a two-step dissolution (or solubilisation) study in aqueous buffers of pH 1.2 followed by pH 6.5. Pharmacokinetic profiles revealed an approximately 1.95-fold increased bioavailability (p=0.02) and a 1.5-fold higher maximum plasma concentration (p=0.14) for Lipoceramic-IBU with reference to Nurofen®. Review of the safety assessments, including physical examinations, clinical laboratory tests and reports of adverse events, confirmed negligible acute side effects related to the administration of blank and ibuprofen-loaded Lipoceramic formulations. This first in man study of a dry lipid and nanoparticle-based formulation successfully demonstrated the safe use and effectiveness of the nanostructured Lipoceramic microparticles in mimicking the food effects for optimising the oral absorption of poorly water-soluble compounds.

Keywords

Lipid-based formulationsSilica nanoparticlesPoorly water-soluble drugsHuman clinical trialBioavailabilityTolerability

Copyright information

© Controlled Release Society 2013

Authors and Affiliations

  1. 1.Ian Wark Research InstituteUniversity of South AustraliaMawson LakesAustralia