Capsule Filling Performance of Powdered Formulations in Relation to Flow Characteristics

Abstract

A successful pharmaceutical capsule filling operation requires a balance of, often conflicting, powder properties – the flowability of the powder, its compressibility, and adequate lubrication to facilitate plug ejection. A powder's flowability is complex and its effect on capsule filling is difficult to predict, but there are dynamic, bulk and shear properties that in combination can provide increased understanding of how powders perform in such processes. This study examines the dosing weight variation and the required ejection force during a capsule filling process for twelve different lactose based formulations and shows how the results correlate with the powder characteristics obtained using a Powder Rheometer. These characteristics include dynamic flowability, bulk density, permeability, compressibility and shear properties. The results clearly show that those formulations containing higher percentage of Acetaminophen (APAP) consistently have higher Specific Energy, Compressibility and Cohesion, along with lower Aeration Ratio – all suggesting higher cohesivity – are associated with higher ejection forces. The powder cohesivity is the dominant factor in relation to the ejection force. Those formulations containing APAP have increased capsule weight variation. However, the formulations containing 10wt.% APAP, showing moderate cohesivity, have consistently higher weight variability than 40wt.% APAP. This is because there is a balance between two separate stages encountered in the filling process – gravity filling and forced filling. Gravity fill is favoured by powders with lower cohesivity and higher permeability. Forced filling is favoured by powders with higher cohesivity and lower permeability.