Aspects into the structural integrity of pharmaceutical bilayer tablets

Bilayer pharmaceutical tablets present a unique medium for more efficient and effective delivery of therapeutics to patients. The bilayer tablet system has several advantages over conventional single layer tablets such as modified drug release, e.g., a fast release layer for immediate therapeutic relief and a slow release layer for continued relief, physical separation of chemically incompatible therapeutics, and treatment of two separate ailments with the use of one tablet. Despite the advantages of bilayer tablets, problems during production and storage can lead to interfacial cracking and delamination which result in unacceptable quality. Failure along the bimaterial interface of a bilayer tablet may occur instantaneously upon ejection from the die or more slowly over time as a result of the absorption of moisture. In order to understand these failure mechanisms there needs to be a better understanding between the mechanical properties of bilayer tablets and the relationship with transient moisture sorption. To solve this problem the solution may be divided into two components: 1) the mechanical understanding of the local stresses around the bilayer interface evolving from the compaction and ejection event, and 2) the understanding of the transient nature of differential moisture sorption into different pharmaceutical materials. This thesis examines the effect of processing parameters and tablet curvature on bilayer tablet integrity. Altering layer order and layer thickness ratio has shown significant changes in the degree of interfacial cracking and the region of crack initiation. A model based on fundamental diffusion mechanisms and basic material properties was developed, solved analytically, and experimentally verified. The 1 D model is capable of predicting the transient moisture uptake process for any porous material with the knowledge of several key material properties. The analytical solution provided the time constant of the diffusion process which is dependent upon overall tablet porosity and the material's ability to absorb moisture. Experimental results on bilayer tablet strength upon exposure to several different humid environments showed that any change from the tablet's original moisture content resulted in a reduction of interfacial strength.