(295f) Gluing Pills: A Novel Approach for Processing of Multi-Layer Tablets

Gluing Pills: A Novel Approach for Processing of Multi-Layer Tablets

¹Sharareh Salar-Behzadi, ¹Sandra Stranzinger, ²Josef Lingitz, ¹Stephan Sacher, ^1,3Johannes Khinast

1- Research Center Pharmaceutical Engineering (RCPE) GmbH, Graz, Austria

2- M & R Automation GmbH, Graz, Austria

3- Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13/3, 8010 Graz Austria

Multi-layer tablet have several advantages over conventional tablets. For example, multi-layer tablet dosage forms can be designed as osmotically-controlled tablets, fixed-dose combinations for delivering incompatible APIs, controlling the releases of multiple APIs at different rates and releasing actives at different sites.

In the production of multi-layer tablets it is critical to control the weight of each layer and to assure a good adhesion between layers. It is also desirable to achieve a clear demarcation plane between the layers, since this is not only appealing but also assures the absence of cross-contamination.

The conventional technology to produce multi-layer tablets is a special rotary press, where each layer has a special compression step. The weight control of this technology is rather complex, making use of either a force control system or tablet thickness. The adhesion between layers is dependent on the material properties and requires a certain surface roughness of the initial layer for particle interlocking and adhesion with the second layer. Furthermore, fines below an average size of 150 microns should be avoided to provide a sharp resolution between the two layers. Problems are often encountered. Inadequate individual layer weight control, disproportionate layers-weight ratio coupled with low drug loads, cross contamination between the layers, insufficient multi-layer tablet hardness and a tendency of delamination of the layers are some of the disadvantages of rotary tablet multi-layer compaction.

In this study we present an innovative approach for the processing of multi-layer tablets. Each layer will be compressed separately, in the form of thin tablet bodies. Then, these tablet bodies will be glued to each other in an automated process. The adhesion between layers depends mainly on the properties of the adhesion gel, physical properties of tablets and the homogeneity of the adhesive layer.

To investigate the impact of these properties, tablets were produced with different excipients and different compaction forces. The impact of potentially critical material attributes (CMA), such as the degree of the plasticity of excipients, particle size distribution, compaction force and punch velocity on critical quality attributes (CQA) of tablets (rawness, specific surface area, hardness and friability), were investigated. Afterwards, these CQAs together with the type of gel binder, its concentration and viscosity were considered as CMAs for glued tablets and their impact on the quality of the adhesion between layers was investigated. Moreover, the penetration and cross-contamination between layers have been studied using a worst case scenario, i.e., tablets with high concentrations of water-soluble API, glued with water soluble gel binder.

This innovative and fast gluing method offers significant advantages, e.g., the ability to control the weight and compaction force in each tableting process, thus avoiding the variability in tablet hardness, disintegration time and dissolution profile of each layer. Moreover, this approach enabled us to design multilayer-tablets with advanced performance and low risk of cross contamination between layers.