Design of experiments approach on the preparation of dry inhaler chitosan composite formulations by supercritical CO2-assisted spray-drying

R. P. Cabral, A. M L Sousa, A. S. Silva, A. I. Paninho, M. Temtem, E. Costa, T. Casimiro, A. Aguiar-Ricardo

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Pulmonary delivery is very attractive as potential route for non-invasive administration of active ingredients to the lungs, by dry powder inhalation, either for directly target the lungs or render a systemic therapeutic effect. Besides biocompatibility, non-toxicity and biodegradability, dry powders must fulfil main particle requirements in terms of performance delivery in order to be considered suitable carriers for dry pulmonary therapeutics, such as size, density and aerodynamic properties. The development of such particles typically involves a complex process of optimization. In this work a design of experiments approach (DoE) was used to study the effect of supercritical CO2-assisted spray-drying (SASD) operational parameters in the final properties of composite chitosan (CHT) microparticles. The effect of CO2 to liquid flow ratio (R), atomization temperature and the co-atomization of a model active ingredient, ibuprofen (IBP), was studied with respect to the particle volumetric diameter (Dv,50), span, mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), geometric standard deviation (GSD) and emitted fraction (EF). The in vitro aerosolization profile of the powders was assessed using an Anderson Cascade Impactor (ACI) equipment able to simulate the deposition of the particles in the lungs. In addition, in vitro release studies from the composite particle formulations were performed and modelled using the Korsmeyer-Peppas equation, as well as lysozyme biodegradation experiments. We were able to develop dry chitosan composite particles with suitable characteristics for the delivery of active ingredients to the lungs. Design of experiments approach was able to statistically correlate the operational conditions with the final characteristics of the formulation.

Original languageEnglish
Pages (from-to)26-35
Number of pages10
JournalJournal of Supercritical Fluids
Publication statusPublished - Oct 2016


  • Chitosan
  • Dry powder
  • DoE
  • Composite particles
  • Pulmonary delivery

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