Solubilizing agents in nasal formulations and their effect on ciliary beat frequency

Toxicol In Vitro. 2012 Feb;26(1):150-6. doi: 10.1016/j.tiv.2011.10.011. Epub 2011 Oct 26.

Abstract

The purpose of this study was to determine the concentration-dependent effect of selected solubilizers, used in common nasal drug formulations, on ciliary beat frequency (CBF) in human nasal epithelial cell cultures. CBF was measured by a high-speed digital imaging method. Excised ciliated human nasal epithelial cells were incubated for 60min with the solubilizers and determination of the half maximal inhibitory concentration (IC(50)), followed by a reversibility test. LDH test was performed on human nasal epithelial cells with the solubilizing agents. These were applied to nasal epithelial cells in IC(50) values. The following rank order in IC(50) values was obtained for the solubilizers: glycerol>propylene glycol>polyethylene glycol 300>N,N-dimethylacetamide>polyethylene glycol 400>ethanol>ethylendiamindihydrochloride>polyvinylpyrrolidon 25>polyvinylpyrrolidon 90. The highest reversibility of approximately 75% was shown by propylene glycol and polyethylene glycol 300 at a concentration of 30% (v/v). Results from the LDH test showed that N,N-dimethylacetamide displayed the highest cytotoxicity with 5.2% at a concentration of 14.5% (v/v). According to these results, several solubilizers can alter the CBF frequency and thus, have an impact on the nasal mucosa. Therefore, CBF studies with solubilizers used at a concentration relevant for nasal formulations are essential in the design of efficient and most notably safe nasal medicinal products.

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemistry, Pharmaceutical
  • Cilia / drug effects*
  • Cilia / physiology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / physiology
  • Humans
  • Inhibitory Concentration 50
  • L-Lactate Dehydrogenase / metabolism
  • Molecular Structure
  • Molecular Weight
  • Nasal Mucosa / cytology*
  • Solvents / chemistry
  • Solvents / toxicity*
  • Viscosity

Substances

  • Solvents
  • L-Lactate Dehydrogenase