Enhancing tabletability of high-dose tablets by tailoring properties of spray-dried insulin particles.

The oral delivery of proteins and peptides provides an attractive dosing option due to its high patient compliance. However, as oral formulations of such macromolecules require the addition of typically poorly compactable permeation enhancers, the compression behaviour in tableting processes can become challenging. In this study, we show that poor compression behaviour can be overcome by tailoring the properties of peptide or protein particles, especially in high-dose tablet formulations. Spray-dried particles with varying particle size and morphology were produced and characterized. The particles were then evaluated for tabletability in well- and poorly tabletable formulations. Tabletability was found to be enhanced most with small and non-hollow spray-dried insulin particles in both formulations. The enhancement was more pronounced in the poorly tabletable formulation than in the well-tabletable one. Thus, the API particle properties play a key role, when evaluating manufacturability of poorly tabletable formulations.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets.