How does secondary processing affect the physicochemical properties of inhalable salbutamol sulphate particles? A temporal investigation

Joana Pinto, Snezana Radivojev, Sarah Zellnitz, Eva Roblegg, Amrit Paudel

Research output: Contribution to journalArticleResearchpeer-review


As pulmonary drug delivery is extended from low doses to high doses, physicochemical characteristics of the active pharmaceutical ingredient gain importance in the development of dry powder inhalers. Therefore, the present work aims to understand the impact of distinct engineering techniques on the process induced physicochemical characteristics of salbutamol sulphate particles over time. The particle engineering techniques chosen were jet-milling and spray-drying, two well used processes in the production of predominately crystalline and amorphous inhalable particles, respectively. Fourier transform infrared spectroscopy, modulated differential scanning calorimetry, particle size distribution and tensiometry experiments were used to characterise the engineered powders immediately, 7, 14 and 21 days after production. The rugged spherical amorphous particles (3.75 ± 0.08 μm) obtained via spray-drying showed that they were capable of forming strong agglomerates (5.01 ± 0.22 μm) through “amorphous bridging”. On the other hand, jet-milling produced smaller (2.06 ± 0.08 μm), crystalline, irregular shaped particles with a very large surface area (11.04 ± 0.10 m2/g) that, over time, formed looser particle aggregates of decreasing size (3.76 ± 0.10 μm). Temporal evolution of the properties of spray-dried and jet milled particles showed a notable influence on the efficiency of blending with a model carrier at 0, 7 and 21 days (e.g. relative standard deviation of drug content of 11.3, 7.0 and 21.6%, respectively).

Original languageEnglish
Pages (from-to)416-428
Number of pages12
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - 7 Aug 2017



  • Adhesive mixtures
  • Amorphous
  • Crystalline
  • Dry powder inhaler (DPI)
  • Inter-particle distance
  • Particle engineering
  • Physicochemical properties
  • Salbutamol sulphate

ASJC Scopus subject areas

  • Pharmaceutical Science

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