Preparation of concentrated stable fenofibrate suspensions via liquid antisolvent precipitation

Mohammad A. Azad, Catharina Knieke, Daniel To, Rajesh Davé

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

A major challenge in achieving size stability for relatively high concentration of fine particles from poorly water-soluble drug fenofibrate (FNB) is addressed through T-mixing based liquid antisolvent precipitation in the presence of ultrasonication and judicious use of stabilizers. Multiple stabilizers were screened in a batch mode prior to their continuous formation via T-mixing. In both cases, the stable suspensions maintained their size after 2 days of storage at room temperature, with the smallest particle size of d50: ∼1.2μm was achieved through a combination of HPMC with SDS or PF-68. The influence of processing parameters, such as sonication energy, sonication probe insert depth and solvent/antisolvent flow rate, on the particle size distribution (PSD) in T-mixing were investigated, to identify optimum processing conditions. Optimal operating and formulation conditions also allowed increase in the drug loading from 0.32% to 4% (w/v), while keeping the median size 2.5μm. Interestingly, the primary particles observed in the SEM were spherical and under 100nm in diameter, indicating agglomeration. It was shown that the stabilized particles could be centrifuged and did not show size growth upon resuspension, allowing for increase in the drug loading up to 27% (w/v), which is a significant novel outcome.

Original languageEnglish (US)
Pages (from-to)1693-1703
Number of pages11
JournalDrug Development and Industrial Pharmacy
Volume40
Issue number12
DOIs
StatePublished - Dec 1 2014

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

Keywords

  • Drug loading
  • Fenofibrate
  • LASP
  • Nanoparticles
  • Stabilization
  • T-mixer

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