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

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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.

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Acknowledgments

The authors gratefully acknowledge the Australian Research Council, the Australian National Health and Medical Research Council, ITEK Pty. Ltd., Bioinnovation South Australia, and the Australian Biotech Ceridia Pty. Ltd. for research funding and support. Specifically, Gregor Rossenberg, Sepehr Shakib and Mark Bruce are acknowledged for assistance and support in undertaking the human clinical trial.

Conflict of interest disclosure

The authors report no conflicts of interest in this work. This study was approved by the Bellberry Human Research Ethics Committee and written informed consent was legally obtained from all subjects.

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Authors and Affiliations

  1. Ian Wark Research Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes, South Australia, 5095, Australia

    Angel Tan, Nasrin Ghouchi Eskandar, Shasha Rao & Clive A. Prestidge

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  1. Angel Tan
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  2. Nasrin Ghouchi Eskandar
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  3. Shasha Rao
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  4. Clive A. Prestidge
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Correspondence to Angel Tan or Clive A. Prestidge.

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Tan, A., Eskandar, N.G., Rao, S. et al. First in man bioavailability and tolerability studies of a silica–lipid hybrid (Lipoceramic) formulation: a Phase I study with ibuprofen. Drug Deliv. and Transl. Res. 4, 212–221 (2014). https://doi.org/10.1007/s13346-013-0172-9

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