Correlation of brittle matrix powder properties to aerodynamic performance of inhaled nintedanib made by thin-film freezing

Tuangrat Praphawatvet, Sawittree Sahakijpijarn, Chaeho Moon, Jay I. Peters, Robert O. Williams

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Nintedanib is a drug approved to treat idiopathic pulmonary fibrosis (IPF) and all chronic progressive fibrosing interstitial lung diseases. Delivery by dry powder inhalation appears to be a potential route to improve efficacy and safety over the oral administration. Inhaled nintedanib powders (TFF-NIN) were produced by thin-film freezing (TFF). The correlation between the physical properties and the aerodynamic performance was evaluated by multivariate correlation analysis presented by the correlation coefficient of each parameter along with its statistical significance. Drug loading and excipients were designed to evaluate the correlation. X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM) demonstrated that TFF produced all formulations of the TFF-NIN as amorphous nintedanib and brittle matrix structures. The physical characteristics of brittle matrix powders, including density, specific surface area (SSA), geometric particle size (Dv50), flowability, powder dispersion, powder deformation, water sorption and moisture content were studied for the correlation with aerodynamic performance. The TFF-NIN powders with high SSA, high flowability, small particle size, high-degree brittle fracture and low moisture content displayed significantly high aerodynamic performance with correlation coefficients over 0.8 (p < 0.05). A higher drug loading decreased the characteristics of brittle matrix powders by increasing particle size and reducing SSA and flowability, which also reduced aerodynamic performance. A higher amount of leucine improved the flowability, SSA, brittle fracture, and aerodynamic performance. In conclusion, the TFF-NIN powders, which exhibited amorphous and brittle matrix morphology, had physical characteristics including SSA, Dv50, flowability, brittle fracture, and moisture content that significantly correlated with aerodynamic performance.

Original languageEnglish (US)
Article number104059
JournalJournal of Drug Delivery Science and Technology
StatePublished - Jan 2023


  • Aerodynamic performance
  • Nintedanib
  • Physical property
  • Pulmonary delivery
  • Pulmonary fibrosis
  • Thin-film freezing

ASJC Scopus subject areas

  • Pharmaceutical Science


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