(206h) The Influence of Roller Compaction Processing Variables on the Rheological Properties of Granules

Pharmaceutical formulations for oral solid dose delivery consist of mixtures of many components, each with a specific role in the optimal delivery of the active pharmaceutical ingredient, (API). In many instances the potency of these APIâ??s means that the actual quantity required per tablet/capsule is extremely small and to ensure content uniformity, a granulation process step is undertaken, especially when some or all of the materials in a formulation have poor flow properties. This approach combines the API with one or more of the other components and is frequently carried out as a wet process. The disadvantages of wet granulation are that the resultant wet mass has to be dried and milled to generate a product that can then be tabletted/encapsulated. These downstream steps are time consuming and incur additional costs; equally some active materials will be unsuitable for the wet processing route due to chemical and/or thermal degradation.

The option to use a dry granulation process, based around a roller compactor and integral mill/screen, has significant benefits both in terms of processing cost reduction but also for use with APIâ??s that cannot be subjected to moisture/solvents and/or heat. Dry granulation is not suitable for all types of powdered material but there is little in the literature that indicates which properties of a formulation make it suitable/unsuitable for this method of processing, with most equipment suppliers and pharmaceutical manufacturers relying on historical and ad-hoc trial information to identify suitable candidate formulations. Equally there is little to indicate which processing parameters produce optimal granulate quality to achieve interruption free processing and high quality products.

However, it is known that the quality of the dry granulate has a significant impact on downstream processes (including mixing and tabletting) and this has been shown to be governed by the rheological properties of the powder. Recent regulatory initiatives on PAT and QbD have also emphasised the need for a greater understanding of all pharmaceutical processes and how input variables, such as variation in powder characteristics, influence process performance.

The main barrier to determining these relationships has been the insensitivity of the methods used historically to characterise the feedstock/granulate properties. Recent developments in automated instrumentation have allowed formulation scientists and engineers to assess powder properties more rapidly and reliably by employing laboratory measurements that simulate the range of process conditions more closely.

This study will show how the processing parameters influence the behaviour of the granulate from a placebo formulation. Granulate was produced using an MacroPactor roller compactor (Gerteis Maschinen + Processengineering AG, Switzerland) where the roller gap, force and speed can be varied together with the screen/sieve size. The powder properties of the feedstock and the granulates were evaluated using an FT4 Powder Rheometer^® (Freeman Technology, UK) to quantify the dynamic, bulk and shear behaviour.

The results clearly demonstrate how several flow properties are influenced by the processing parameters â?? particularly the permeability; compressibility; aeration and dynamic properties which all showed close correlation with several modes of operation of the roller compactor. These granulate properties have also been shown to correlate closely with variance in die filling and tablet strength. This study emphasises that the tools are available to fully specify the design space for pharmaceutical powder processing unit operations. This allows equipment suppliers and powder processors to better understand the design, control and operation of their manufacturing trains so that they can take account of batch-to-batch variation in feedstocks, changes to feedstock suppliers, re-formulation and assessing suitability for completely different products.