Drug/lactose co-micronization by jet milling to improve aerosolization properties of a powder for inhalation

Int J Pharm. 2006 Sep 14;321(1-2):162-6. doi: 10.1016/j.ijpharm.2006.05.009. Epub 2006 May 12.

Abstract

The aim of this work was to formulate a powder for inhalation with fusafungine, a drug substance initially highly cohesive. The classical approach based on micronization by jet milling to prepare respirable drug particles and then blending with a carrier was first applied. A fractional factorial experimental design was implemented to screen six formulation parameters. The effect of drug/lactose co-micronization on aerosolization was then evaluated. In vitro deposition studies were performed with the twin stage glass impinger and the inhaler Spinhaler. Micronization did not induce DSC-detectable amorphization and gave a highly cohesive, poor flowable powder with a theoretical aerodynamic diameter of 5 microm. The powder was then blended with coarse lactose and optionally fine lactose. Unfortunately, the respirable fraction could not be optimized and remained below 10%. On the other hand, a co-micronized powder drug/fine lactose 50:50 gave a respirable fraction of 16%. Following blending with a carrier, the respirable fraction and the emitted dose fraction reached 23% and 69%, respectively. The use of a fine lactose grade for co-micronization was essential. In conclusion, this study demonstrated that co-micronization with a fine lactose is an efficient and simple strategy to formulate a powder for inhalation with enhanced aerosolization properties, especially for highly cohesive drug substance.

MeSH terms

  • Administration, Inhalation
  • Aerosols*
  • Chemistry, Pharmaceutical
  • Lactose / administration & dosage*
  • Powders
  • Technology, Pharmaceutical*

Substances

  • Aerosols
  • Powders
  • Lactose