(346e) Mechanistic Characterization of Bilayer Tablets. II: The Effect of Layer Sequence and Fracture Surface Topography

Bilayer tablets have some key advantages compared to conventional monolayer tablets. For instance, such tablets are commonly used to avoid chemical incompatibilities of formulation components by physical separation. In addition, bilayer tablets have enabled the development of controlled delivery of active pharmaceutical ingredients with pre-determined release profiles by combining layers with various release patterns, or by combining slow-release with immediate-release layers. However, these drug delivery devices are mechanically complicated to design/manufacture and harder to predict their long term mechanical properties due to the poor mechanical and compression characteristics of the constituent materials in the compacted adjacent layers, elastic mismatch of the layers, insufficient hardness, inaccurate individual mass control, cross contamination between the layers, reduced yield, and their tendency to delaminate at the interface between the adjacent compacted layers during and after the various stages of production downstream of the compaction process. Therefore, the major problem, that has to be overcome, is to understand in detail the sources of these problems in micro- and macro-scales and to develop remedies to solve them during solid dosage delivery design.

Bilayer tablets of the widely used excipients microcrystalline cellulose (MCC) and pregelatinised starch using unlubricated and lubricated punch and die sets were manufactured. The objectives of this presentation were three-fold: (i) to explore the effect of tableting conditions on the interfacial and individual layer strengths of bilayer tablets; (ii) to assess different fracture patterns related to the mechanical and fracture surface properties of compacted adjacent layers; and (iii) to determine the influence of layer sequence on the mechanical performance of bilayer tablets. In the reported experiments, using a developed tensile stress method, bilayer tablets were debonded to determine the fracture and axial tensile strength values. Fracture surfaces and topographic profiles of the debonded tablets were studied. Different fracture patterns, namely, clear layer break, half-half break, cap-shape break, and clear interface break were observed as a function of various initial and final compaction pressures. X-ray micro-computed tomography (µCT) also was utilized to examine the influence of localized density distribution on the delamination phenomena of bilayer tablets. The tensile strength values of individual layers after debonding were also determined and compared. It was observed that the bilayer tablets produced in a lubricated die fail at the interface while the tablets produced in an unlubricated die fail as half-half, cap-shape and clear layer breaks. Also it was shown why the layer sequence plays such a key role in the mechanical integrity of the bilayer tablets. It was found that, using the same compaction process, the tensile strength of the tablets with starch as the initial and MCC as the final layer were substantially higher than those of MCC as the initial and starch as the final layer. Fracture patterns and topographic profiles coupled with the X-ray µCT have provided a great insight into the effect of tableting conditions, individual layer properties, cross-contamination between adjacent layers, layer sequence, and stress distribution in bilayer tablets.