Gluing Pills Technology: A novel route to multilayer tablet manufacturing.

Layer weight control, delamination and cross-contamination are major challenges in the production of compacted multilayer tablets (MLT). In this work, we describe a novel approach to manufacturing MLT: the Gluing Pills Technology (GPT). High loads of ibuprofen free acid and caffeine anhydrate were blended with microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCPD) and compacted into monolayer tablets. They were glued together via the GPT using solutions of either fish gelatin or polyvinylpyrrolidone K90 as gluing agents with defined viscosity. Factors that have a substantial impact on the deformation behavior of blends (i.e., elastic recovery, tensile strength and porosity) of monolayer tablets were investigated in terms of bilayer tablets manufactured via the GPT. The results indicated that high levels of elastic recovery negatively affected the robustness of GPT bilayer tablets and that the type of gluing agent was critical. Raman microscopy analysis was successfully applied to qualitatively assess the function of gluing layer as a barrier to cross-contamination between two monolayer tablets. This study shows the feasibility of the GPT for manufacturing of robust MLT, emphasizing its potential in terms of real-time production of individualized fixed-dose combinations and application in both translational pharmaceutics and personalized medicine.