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.

Critical assessment of inverse gas chromatography as means of assessing surface free energy and acid-base interaction of pharmaceutical powders.

Inverse gas chromatography (IGC) has been employed as a research tool for decades. Despite this record of use and proven utility in a variety of applications, the technique is not routinely used in pharmaceutical research. In other fields the technique has flourished. IGC is experimentally relatively straightforward, but analysis requires that certain theoretical assumptions are satisfied. The assumptions made to acquire some of the recently reported data are somewhat modified compared to initial reports. Most publications in the pharmaceutical literature have made use of a simplified equation for the determination of acid/base surface properties resulting in parameter values that are inconsistent with prior methods. In comparing the surface properties of different batches of alpha-lactose monohydrate, new data has been generated and compared with literature to allow critical analysis of the theoretical assumptions and their importance to the interpretation of the data. The commonly used (simplified) approach was compared with the more rigorous approach originally outlined in the surface chemistry literature.