On the influence of raw material attributes on process behaviour and product quality in a continuous WET granulation tableting line

Abstract

Continuous manufacturing of oral solids is a complex process in which critical material attributes (CMAs), formulation and critical process parameters (CPPs) play a fundamental role. However, assessing their effect on the intermediate and final product’s critical quality attributes (CQAs) remains challenging. The aim of this study was to tackle this shortcoming by evaluating the influence of raw material properties and formulation composition on the processability and quality of granules and tablets on a continuous manufacturing line. Powder-to-tablet manufacturing was performed using four formulations in various process settings. Pre-blends of different drug loadings (2.5 % w/w and 25% w/w) and two BCS classes (Class I and II) were continuously processed on an integrated process line ConsiGmaTM 25, including twin screw wet granulation, fluid bed drying, milling, sieving, in-line lubrication and tableting. The liquid-to-solid ratio and the granule drying time were varied to process granules under nominal, dry and wet conditions. It was shown that the BCS class and the drug dosage influenced the processability. Intermediate quality attributes, such as the loss on drying and the particle size distribution, directly correlated with the raw material’s properties and process parameters. Process settings had a profound impact on the tablet’s hardness, disintegration time, wettability and porosity.