Abstract
The oral drug delivery system using bilayer tablets has become more commonly used in therapeutic strategies as it has several advantages over conventional single layer tablets such as the modified drug release, physical separation of chemically incompatible therapeutics, elongation of product patent life, etc. However, one of the common problems associated with bilayer tablets is the insufficient interfacial strength between layers, which may lead to product failure during the manufacturing process. Therefore, it is important to gain a good understanding on bilayer technology to bring bilayer design and manufacturing to similar levels of robustness as encountered in single layer tablets. In this thesis, the attributes (e.g. compressibility, elasticity, compactibility and hygroscopicity) of the commonly used pharmaceutical powders were firstly investigated to thoroughly understand how these mechanical properties affect the manufacturing performance and product quality, which built a sound scientific basis for formulation design. Based on the material property investigation, a plastic powder (MCC PH 102) and a brittle material (mannitol SD 100) were selected to produce bilayer tablets. The interfacial strength of these tablets was evaluate using two different methods: direct tensile test and terahertz pulsed imaging system. The tablet interfacial strength was used in the analysis to investigate the impacts of the different factors on tablet integrity. For instance, the influences of both powder conditions (e.g. powder formulation, mean particle size and water content) and manufacturing process conditions (e.g. compression pressure, dwell time and punch geometry) on bilayer tablet interfacial strength were examined. In addition, the elastic contact theory was also used to model the particulate contacts at the bilayer tablet interface.