Head-To-Head Comparison of Different Solubility-Enabling Formulations of Etoposide and Their Consequent Solubility-Permeability Interplay

Avital Beig, Jonathan M. Miller, David Lindley, Robert A. Carr, Philip Zocharski, Riad Agbaria, Arik Dahan

Research output: Contribution to journalArticlepeer-review


The purpose of this study was to conduct a head-to-head comparison of different solubility-enabling formulations, and their consequent solubility-permeability interplay. The low-solubility anticancer drug etoposide was formulated in several strengths of four solubility-enabling formulations: hydroxypropyl-β-cyclodextrin, the cosolvent polyethylene glycol 400 (PEG-400), the surfactant sodium lauryl sulfate, and an amorphous solid dispersion formulation. The ability of these formulations to increase the solubility of etoposide was investigated, followed by permeability studies using the parallel artificial membrane permeability assay (PAMPA) and examination of the consequent solubility-permeability interplay. All formulations significantly increased etoposide's apparent solubility. The cyclodextrin-, surfactant-, and cosolvent-based formulations resulted in a concomitant decreased permeability that could be modeled directly from the proportional increase in the apparent solubility. On the contrary, etoposide permeability remained constant when using the ASD formulation, irrespective of the increased apparent solubility provided by the formulation. In conclusion, supersaturation resulting from the amorphous form overcomes the solubility-permeability tradeoff associated with other formulation techniques. Accounting for the solubility-permeability interplay may allow to develop better solubility-enabling formulations, thereby maximizing the overall absorption of lipophilic orally administered drugs.

Original languageAmerican English
Pages (from-to)2941-2947
Number of pages7
JournalJournal of Pharmaceutical Sciences
Issue number9
StatePublished - 1 Sep 2015


  • BCS
  • intestinal permeability
  • oral drug absorption
  • solubility-enabling formulations
  • solubility-permeability interplay

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science


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