Challenges in technology of bilayer and multi-layer tablets: a mini-review

Abstract

Bilayer and multi-layer tablets are enjoying growing popularity among original drug and generic product manufacturers. Multi-layer tablets have many key benefits compared to classic immediate-release tablets. The use of such solid oral dosage forms simplifies dosing regimens in combination therapy, and thus improves patient compliance. However, the technology of multilayer tablets is demanding and requires precise choice of excipients and production parameters with regard to each technological step. The main benefits of multi-layer tablets, certain aspects of their production and the challenges encountered during the compression process are reviewed in this paper.

Pharmacotechnical Development and Optimization of Multilayered Tablets: An Updated Industrial Review With Emphasis on Bilayer Tablets

“…Hence, it is preferable to have a certain level of weight similarity between the adjacent layers in order to obtain multilayers with acceptable physical and mechanical properties, as well as similar compaction profiles. However, it is often not possible to maintain a similar weight ratio between individual layers for either formulation or therapeutic reasons [17,43]. On the other hand, the ratio between individual layers and the sequence of their arrangements plays a key role in reducing the potential of intralayer capping and interlayer delamination, as in the case of bilayer tablets, where the optimal weight ratio between individual layers is 1:1 or 1:2, and sometimes it extends to 1:3 or even 1:4 [16,17].…”

“…Thus, there is no possibility to avoid common problems associated with the first layer compression. It is also preferable to use materials with a higher fragmentation tendency to formulate the first layer, and materials with a greater elastic-plastic deformation capacity in formulating other layers [40,43].…”

“…Yang et al [52] concluded that an increase in the punch speed between 50 to 500 mm/sec significantly decreased the porosity on each individual layer. Generally, the compression force of the first layer is set to be around 2-18 kN in order to lamp the powders/granules to diminish the volume and create more space for depositing the second layer [43]. In fact, high compression forces may lead to an increase the tensile strength and decrease surface roughness [43].…”

“…Generally, the compression force of the first layer is set to be around 2-18 kN in order to lamp the powders/granules to diminish the volume and create more space for depositing the second layer [43]. In fact, high compression forces may lead to an increase the tensile strength and decrease surface roughness [43]. Alternatively, surface smoothness of the first layer may also lead to an increase the possibility of delamination by limiting the intramolecular adherence between the adjacent layers [16].…”