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

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

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)212-221
Number of pages10
JournalDrug Delivery and Translational Research
Volume4
Issue number3
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Bioavailability
  • Human clinical trial
  • Lipid-based formulations
  • Poorly water-soluble drugs
  • Silica nanoparticles
  • Tolerability

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