Co-spray-dried urea cross-linked hyaluronic acid and sodium ascorbyl phosphate as novel inhalable dry powder formulation

Arianna Fallacara, Laura Busato, Michele Pozzoli, Maliheh Ghadiri, Hui Xin Ong, Paul M. Young, Stefano Manfredini, Daniela Traini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The pathogenesis and progression of several lung disorders is propagated by inflammatory and oxidative processes, which can be controlled by adjunctive inhaled therapies. The present study aimed to develop an inhalable dry powder formulation consisting of co-spray-dried urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate (SD HA-CL–SAP), a novel combination which was recently shown to possess anti-inflammatory, antioxidant, and wound healing properties. Native HA and SAP were co-spray dried (SD HA–SAP) and evaluated as control formulation. Yield (Y%) and encapsulation efficiency (EE%) were 67.0 ± 4.8% and 75.5 ± 7.2% for SD HA–SAP, 70.0 ± 1.5% and 66.5 ± 5.7% for SD HA-CL–SAP, respectively. Both formulations were shown to be suitable for lung delivery in terms of morphology, particle size (median volumetric diameter ∼ 3.4 μm), physical and thermal stability, in vitro aerosol performance - respirable fraction: 30.5 ± 0.7% for SD HA–SAP and 35.3 ± 0.3% for SD HA-CL–SAP. SAP release was investigated using Franz cells and air-interface Calu-3 cell model (>90% of SAP transported within 4 h). The innovative SD HA-CL–SAP formulation holds potential as inhalable dry powder for the treatment of inflammatory lung disorders.

Original languageEnglish
Pages (from-to)2964-2971
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number9
Publication statusPublished - Sep 2019
Externally publishedYes


  • aerosol performance
  • hyaluronic acid
  • inhalable dry powder
  • pulmonary drug delivery
  • sodium ascorbyl phosphate
  • urea-crosslinked hyaluronic acid


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