Comminution-amorphisation relationships during ball milling of lactose at different milling conditions

Int J Pharm. 2017 Aug 7;528(1-2):215-227. doi: 10.1016/j.ijpharm.2017.05.043. Epub 2017 May 22.

Abstract

The purpose of the study was to investigate the relationship between comminution and amorphisation of α-lactose monohydrate particles during ball milling under different milling conditions, including ball-to-powder mass ratio, milling time and ball diameter. The results revealed that at a constant ball filling ratio, ball-to-powder mass ratio of 25:1 resulted in the lowest minimum particle diameter of ∼5μm and the highest degree of apparent amorphous content of 82%. The rate of comminution was high during early stage of milling whereas the degree of apparent amorphous content increased gradually at a slow rate. An increased ball-to-powder mass ratio during milling increased both the rate of comminution and the rate of amorphisation. Using a given ball-to-powder mass ratio, the ball diameter affected the degree of apparent amorphous content of the particles while the particle diameter remained unchanged. The relationship between comminution and amorphisation could be described as consisting of two stages, i.e. comminution dominated and amorphisation dominated stage. It was proposed that the rate constant of comminution and amorphisation are controlled by stress energy distribution in the milling jar and the stress energy distribution is regulated by the ball motion pattern that can be affected by the process parameter used.

Keywords: Amorphisation; Ball milling; Comminution; Comminution rate constant; Process-induced disordering; Stress energy distribution; α-lactose monohydrate.

MeSH terms

  • Drug Compounding*
  • Lactose / analysis*
  • Particle Size
  • Powders*

Substances

  • Powders
  • Lactose