Comparison of specific surface areas of a micronized drug substance as determined by different techniques

Abstract

Drug Substance (DS) Specific Surface Area (SSA), porosity and Particle Size Distribution (PSD) are important physical characteristics for pharmaceutical applications. For instance the DS surface area can greatly influence the dissolution rate which, in turn, might affect bioavailability. Several analytical methods can be used to characterise the DS and determine the powder SSA: measurements by gas adsorption (BET method) and gas permeametry (Blaine Fisher method) and calculation from PSD obtained by laser light scattering or from Mercury Intrusion Porosimetry (MIP) curves. In this study we have compared surface areas measured by gas permeametry or gas adsorption with SSA calculated from PSD obtained by laser light scattering or from MIP curves for the case of a low specific surface area micronized DS (SSA in the range of 1 to 3 m 2 /g). Correlation between specific surface areas measured using a simple and robust technique such as gas permeametry and SSA determined by more sophisticated techniques such as PSD, MIP and BET have been carried out. A good agreement between S BF (surface measured by gas permeametry, Blaine Fisher, S BF ) and measured S BET was obtained. This is due to the fact that the DS studied does not exhibit intraparticular microporosity (both Krypton and air can access all the surface developed by the powder). SBF compared with estimated S Hg (estimated from MIP results) and S PSD (estimated from PSD results) show a good linearity, but S Hg and S PSD values are overestimated. This arises due to the simplifying approximations for particles shape included in the theoretical models for PSD and PIM. Although BF provides a direct SSA measurement, the techniques of PSD, MIP and gas adsorption provide complementary information on texture characteristics to better understand and interpret results from process and formulation development studies. However, in some cases, BF can be considered as a complete and adequate quality control method which can easily be set to work within the frame work of production control provided that the method has been validated and applies well to the powder studied.