Mechanical Characterization of Pharmaceutical Powders by Nanoindentation and Correlation with Their Behavior during Grinding

Controlling the size of powder particles is pivotal in the design of many pharmaceutical forms and the related manufacturing processes and plants. One of the most common techniques for particle size reduction in the process industry is powder milling, whose efficiency relates to the mechanical properties of the powder particles themselves. In this work, we first characterize the elastic and plastic responses of different pharmaceutical powders by measuring their Young modulus, the hardness, and the brittleness index via nano-indentation. Subsequently, we analyze the behavior of those powder samples during comminution via jet mill in different process conditions. Finally, the correlation between the single particle mechanical properties and the milling process results is illustrated; the possibility to build a predictive model for powder grindability, based on nano-indentation data, is critically discussed

Combining formulation and process aspects for optimizing the high-shear wet granulation of common drugs

The purpose of this research was to determine the effects of some important drug properties (such as particle size distribution, hygroscopicity and solubility) and process variables on the granule growth behaviour and final drug distribution in high shear wet granulation. Results have been analyzed in the light of widely accepted theories and some recently developed approaches. A mixture composed of drug, some excipients and a dry binder was processed using a lab-scale high- shear mixer. Three common active pharmaceutical ingredients (paracetamol, caffeine and acetylsalicylic acid) were used within the initial formulation. Drug load was 50% (on weight basis). Influences of drug particle properties (e.g. particle size and shape, hygroscopicity) on the granule growth behaviour were evaluated. Particle size distribution (PSD) and granule morphology were monitored during the entire process through sieve analysis and scanning electron microscope (SEM) image analysis. Resistance of the wet mass to mixing was furthermore measured using the impeller torque monitoring technique. The observed differences in the granule growth behaviour as well as the discrepancies between the actual and the ideal drug content in the final granules have been interpreted in terms of dimensionless quantity (spray flux number, bed penetration time) and related to torque measurements. Analysis highlighted the role of liquid distribution on the process. It was demonstrated that where the liquid penetration time was higher (e.g. paracetamol-based formulations), the liquid distribution was poorer leading to retarded granule growth and selective agglomeration. On the other hand where penetration time was lower (e.g. acetylsalicylic acid-based formulations), the growth was much faster but uniformity content problem arose because of the onset of crushing and layering phenomena