Enhanced physical stabilization of fenofibrate nanosuspensions via wet co-milling with a superdisintegrant and an adsorbing polymer

Mohammad Azad, Afolawemi Afolabi, Anagha Bhakay, Jonathan Leonardi, Rajesh Davé, Ecevit Bilgili

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Drug nanoparticles in suspensions can form aggregates leading to physical instability, which is traditionally mitigated using soluble polymers and surfactants. The aim of this paper was to explore common superdisintegrants, i.e., sodium starch glycolate (SSG), croscarmellose sodium (CCS), and crospovidone (CP), as novel class of dispersants for enhanced stabilization of fenofibrate (FNB), a model BCS Class II drug, suspensions. FNB was wet-milled with superdisintegrants along with hydroxypropyl methylcellulose (HPMC), a soluble adsorbing polymer, in a stirred media mill. For comparison, FNB was also milled in the presence of HPMC and/or SDS (sodium dodecyl sulfate) without superdisintegrants. Laser diffraction, scanning electron microscopy, viscometry, differential scanning calorimetry, and powder X-ray diffraction were used to characterize the suspensions. The results show that 2% HPMC along with 1% SSG or 1% CCS mitigated the aggregation of FNB nanoparticles significantly similar to the use of either 5% HPMC or 1% HPMC-0.075% SDS, whereas CP was not effective due to its low swelling capacity. CCS/SSG enhanced steric-kinetic stabilization of the FNB suspensions owing to their high swelling capacity, viscosity enhancement, and physical barrier action. Overall, this study provides a mechanistic basis for a novel method of formulating surfactant-free drug nanosuspensions with co-milled superdisintegrants.

Original languageEnglish (US)
Pages (from-to)372-385
Number of pages14
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume94
DOIs
StatePublished - Jul 6 2015

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Keywords

  • Drug nanoparticles
  • Physical stability
  • Superdisintegrants
  • Surfactant-free
  • Swelling
  • Wet media milling

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