(346a) Challenges in Developing A Bilayer Tablet

In the last decade, interest in developing a combination of two or more Active Pharmaceutical Ingredients (API) in a single dosage form (bilayer tablet) has increased in the pharmaceutical industry, promoting patient convenience and compliance. Bilayer tablets can be a primary option to avoid chemical incompatibilities between API by physical separation, and to enable the development of different drug release profiles (immediate release with extended release). Despite their advantages, due to the use of different materials and complex geometric boundaries between the adjacent layers, the mechanical structures of this drug delivery system have become quite intricate, requiring complicated tablet architectures as well as patient-friendly administration which pose serious challenges to the pharmaceutical scientists/engineers. This oral presentation details the major challenges associated with bilayer compression and rational strategy to deliver the desired bilayer tablet performance.

One of the major challenges is lack of sufficient bonding and adhesion at the interface between the adjacent compacted layers which is often the result of an interfacial crack driven by residual stresses in the tablet propagating a finite distance within the tablet and leads to delamination (layer-separation) which may not always be apparent immediately after compaction (e.g., during storage, packaging, shipping). In addition, if the compacted layers are too soft or too hard, they will not bond securely with each other which can lead to compromised mechanical integrity. Other challenges during development include establishing the order of layer sequence, layer weight ratio, elastic mismatch of the adjacent layers, first layer tamping force, and cross contamination between layers. These factors, if not well controlled/optimized, in one way or another will impact the bilayer compression per se (inefficient or uncontrolled process) and the quality attributes of the bilayer tablets (sufficient mechanical strength to maintain its integrity and individual layer weight control). Therefore, it is critical to obtain an insight into the root causes to enable design of a robust product and process.

Since the adjacent compacted layers of a bilayer tablet are bonded together by mechanical means, understanding what influences the stress state, the mechanical properties of each layer and the resultant bilayer tablet, and compression parameters along with specialized techniques to predict failure as a function of layer properties and compression conditions are primordial to successfully developing bilayer tablets.