Nasal Powder Formulation of Tranexamic Acid and Hyaluronic Acid for the Treatment of Epistaxis

Pharm Res. 2020 Sep 4;37(10):186. doi: 10.1007/s11095-020-02913-w.

Abstract

Purpose: The aim of this study was to develop a nasal powder formulation of the antifibrinolytic drug, tranexamic acid (TXA), in combination with the wound-healing agent hyaluronic acid (HA) for the local treatment of epistaxis (nose bleeding).

Methods: Formulations of TXA alone and with different concentrations of HA were freeze-dried and characterised according to their physicochemical properties. Aerosol performance was assessed to ensure nasal deposition with minimal lung deposition. Nasal epithelial cells were used to assess cytotoxicity, transport across the nasal epithelium, antioxidant, wound-healing and anti-inflammatory properties of all formulations.

Results: Formulations containing TXA and HA were produced and found to be mostly deposited in the nasal cavity (more than 90%). Formulation of TXA + 0.3%HA showed wound reduction of 29.3% when assessed in ALI culture. At this concentration, formulations also reduced ROS production in RPMI 2650, and IL-8 production in primary nasal epithelial cells. Furthermore, for formulations containing HA, the higher viscosity may lead to larger residence time in the nasal cavity.

Conclusions: Combination of TXA with HA shows promising results for the treatment of nasal epistaxis.

Keywords: epistaxis; formulation; nasal cells; nose bleeding; wound healing.

MeSH terms

  • Administration, Intranasal
  • Aerosols
  • Antifibrinolytic Agents / administration & dosage
  • Antifibrinolytic Agents / chemistry
  • Antifibrinolytic Agents / therapeutic use*
  • Cell Line
  • Drug Combinations
  • Drug Compounding
  • Epistaxis / drug therapy*
  • Freeze Drying
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / therapeutic use*
  • Interleukin-8 / biosynthesis
  • Lung / metabolism
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism
  • Powders
  • Reactive Oxygen Species
  • Tranexamic Acid / administration & dosage
  • Tranexamic Acid / chemistry
  • Tranexamic Acid / therapeutic use*
  • Wound Healing / drug effects

Substances

  • Aerosols
  • Antifibrinolytic Agents
  • CXCL8 protein, human
  • Drug Combinations
  • Interleukin-8
  • Powders
  • Reactive Oxygen Species
  • Tranexamic Acid
  • Hyaluronic Acid