The influence of lactose on the powder behavior and aerodynamic performance of bosentan microparticles for dry powder inhalation

Abstract

In this study, we prepared carrier-based formulations for dry powder inhalers by mixing bosentan microparticles with carrier, prepared in three separate types of lactose. Spray-dried, milled and sieved lactose resulted in formulations with various shapes, surface morphology and particle size distributions. In the spray-dried lactose, the micronized bosentan particles were trapped and strongly interlocked in the rugged surface of spray-dried lactose, whereas in the milled and sieved lactose they exhibited lower binding affinity onto the smooth surface of carrier. In all of the carrier-based formulations, the flow properties were improved compared with bosentan microparticles alone, in the following order spray-dried, sieved and milled lactose. The aerodynamic characteristics of each were evaluated by particle image velocimetry and Andersen cascade impactor™. Depending on the lactose carrier type, particle dispersion showed different flow characteristics. In the spray-dried lactose, the formulation was dispersed fast in the only frontal direction, while the milled and sieved lactose formulations formed a relatively slower S-shaped and fountain-shaped flow stream, respectively. In addition, milled and sieved lactose formulations showed that the drug particles were readily liberated from the lactose carrier, and demonstrated significantly higher aerosol performance than spray-dried lactose.

 

Conclusion

In order to overcome the cohesiveness of micronized drug particles, we prepared several carrierbased formulations containing BM. In all cases, the homogeneity was ensured and the flow properties were improved over BM alone, which could enhance the handling, processing and emission from device. The particular properties of lactose carriers such as shape, roughness and particle size distribution significantly affected aerodynamic properties identified with PIV and ACI test. The lactose carriers that showed relatively irregular shape, smooth surface and polydisperse size are beneficial to the aerosol performance of the BM. Results of this study indicate that not only delivery efficiency but also dose reproducibility and producibility of dry powder formulations containing bosentan can be enhanced.

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Graphic with process and results  to use bosentan microparticles for dry powder inhalation
Dry powder inhalers formulation and aerosol performance

Armor Pharma – Excipure DPI Lactose

EXCIPURE™  lactose for Dry powder Inhalation 

Our state of the art industrial facility, located in Brittany, FRANCE, is in full compliance with pharmaceutical standards ( EXCiPACT, cGMP, GDP, PAT) and enables the production of lactose in line with pharmaceutical regulations: Ph-EU, USP-NF, and JP.