Influence of micronization on the compaction properties of an investigational drug using tableting index analysis

Abstract

Tableting index analysis was used to study the compaction properties of two lots of an investigational drug substance alone and in combination with excipients in tablet formulations. Lot A was pin-milled while lot B was micronized using a fluid energy mill. Light scattering analysis demonstrated a median particle size of 23.4 and 5.0 μm for lots A and B, respectively. Results from tableting index analysis indicated a significantly higher average tensile strength and bonding index for the micronized material at solid fractions of 0.80, 0.85, and 0.90. The enhanced bonding could be attributed to approximately a five-fold increase in particle surface area and associated increase in the true contact areas between the micronized particles. Brittle fracture index testing demonstrated slightly higher brittle propensities for the pure micronized compacts at each solid fraction. Tableting index analysis was also performed on tableting formulations containing milled and micronized drug at both the 30 and 65% level. The formulation containing 65% micronized drug demonstrated a significantly higher bonding index over the equivalent formulation containing milled drug. However, there was minimal difference in the bonding index between the formulations containing 30% micronized and milled drug substance. Results suggested that the incorporation of micronized drug could significantly increase the bonding propensities of high dose formulations in comparison with formulations containing conventionally milled drug substance. In addition, tableting index analysis was shown to be a very useful technique to quantitatively study the effect of micronization on compaction properties of tableting formulations. © 1997 Elsevier Science B.V. All rights reserved