Investigation into the manufacture and properties of inhalable high-dose dry powders produced by comilling API and lactose with magnesium stearate

Michael Lau, Paul M. Young, Daniela Traini*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

The aim of the study was to understand the impact of different concentrations of the additive material, magnesium stearate (MGST), and the active pharmaceutical ingredient (API), respectively, on the physicochemical properties and aerosol performance of comilled formulations for high-dose delivery. Initially, blends of API/lactose with different concentrations of MGST (1–7.5% w/w) were prepared and comilled by the jet-mill apparatus. The optimal concentration of MGST in comilled formulations was investigated, specifically for agglomerate structure and strength, particle size, uniformity of content, surface coverage, and aerosol performance. Secondly, comilled formulations with different API (1–40% w/w) concentrations were prepared and similarly analyzed. Comilled 5% MGST (w/w) formulation resulted in a significant improvement in in vitro aerosol performance due to the reduction in agglomerate size and strength compared to the formulation comilled without MGST. Higher concentrations of MGST (7.5% w/w) led to reduction in aerosol performance likely due to excessive surface coverage of the micronized particles by MGST, which led to failure in uniformity of content and an increase in agglomerate strength and size. Generally, comilled formulations with higher concentrations of API increased the agglomerate strength and size, which subsequently caused a reduction in aerosol performance. High-dose delivery was achieved at API concentration of >20% (w/w). The study provided a platform for the investigation of aerosol performance and physicochemical properties of other API and additive materials in comilled formulations for the emerging field of high-dose delivery by dry powder inhalation.

Original languageEnglish
Pages (from-to)2248-2259
Number of pages12
JournalAAPS PharmSciTech
Volume18
Issue number6
DOIs
Publication statusPublished - 1 Aug 2017
Externally publishedYes

Keywords

  • comilling
  • dry powder
  • high-dose delivery
  • jet-mill
  • magnesium stearate

Fingerprint

Dive into the research topics of 'Investigation into the manufacture and properties of inhalable high-dose dry powders produced by comilling API and lactose with magnesium stearate'. Together they form a unique fingerprint.

Cite this