Orthogonal frequency division multiplexing with
index modulation (OFDM-IM), which uses the subcarrier indices
as a source of information, has attracted considerable interest
recently. Motivated by the index modulation (IM) concept, we
build a circular convolution filter bank multicarrier with index
modulation (C-FBMC-IM) system in this paper. The advantages
of the C-FBMC-IM system are investigated by comparing the
interference power with the conventional C-FBMC system. As
some subcarriers carry nothing but zeros, the minimum mean
square error (MMSE) equalization bias power will be smaller
comparing to the conventional C-FBMC system. As a result,
our C-FBMC-IM system outperforms the conventional C-FBMC
system. The simulation results demonstrate that both BER and
spectral efficiency improvement can be achieved when we apply
IM into the C-FBMC system.
As one of the commonly-used solid dosage forms, pharmaceutical tablets have been widely
used to deliver active drugs into the human body, satisfying patient?s therapeutic requirements.
To manufacture tablets of good quality, diluent powders are generally used in formulation
development to increase the bulk of formulations and to bind other inactive ingredients with the active
pharmaceutical ingredients (APIs). For formulations of a low API dose, the drug products generally
consist of a large fraction of diluent powders. Hence, the attributes of diluents become extremely
important and can significantly influence the final product property. Therefore, it is essential to
accurately characterise the mechanical properties of the diluents and to thoroughly understand how
their mechanical properties affect the manufacturing performance and properties of the final products,
which will build a sound scientific basis for formulation design and product development. In this
study, a comprehensive evaluation of the mechanical properties of the widely-used pharmaceutical
diluent powders, including microcrystalline cellulose (MCC) powders with different grades (i.e.,
Avicel PH 101, Avicel PH 102, and DG), mannitol SD 100, lactose monohydrate, and dibasic calcium
phosphate, were performed. The powder compressibility was assessed with Heckel and Kawakita
analyses. The material elastic recovery during decompression and in storage was investigated
through monitoring the change in the dimensions of the compressed tablets over time. The powder
hygroscopicity was also evaluated to examine the water absorption ability of powders from the
surroundings. It was shown that the MCC tablets exhibited continuous volume expansion after
ejection, which is believed to be induced by (1) water absorption from the surrounding, and (2) elastic
recovery. However, mannitol tablets showed volume expansion immediately after ejection, followed
by the material shrinkage in storage. It is anticipated that the expansion was induced by elastic
recovery to a limited extent, while the shrinkage was primarily due to the solidification during
storage. It was also found that, for all powders considered, the powder compressibility and the
elastic recovery depended significantly on the particle breakage tendency: a decrease in the particle
breakage tendency led to a slight decrease in the powder compressibility and a significant drop in
immediate elastic recovery. This implies that the particle breakage tendency is a critical material
attribute in controlling the compression behaviour of pharmaceutical powders.
Thermal properties of powders are critical material attributes that control temperature rise during tableting and roll compaction. In this study, various analytical methods were used to measure the thermal properties of widely used pharmaceutical excipients including microcrystalline cellulose (MCC) of three different grades (Avicel PH 101; Avicel PH 102 and Avicel DG), lactose and mannitol. The effect of relative density on the measured thermal properties was investigated by compressing the powders into specimen of different relative densities. Differential thermal analysis (DTA) was employed to explore endothermic or exothermic events in the temperature range endured during typical pharmaceutical manufacturing processes, such as tabletting and roll compaction. Thermogravimetric analysis (TGA) was performed to analyse the water/solvent content, either in the form as solvates or as loosely bound molecules on the particle surface. Thermal conductivity analysis (TCA) was conducted to measure thermal conductivity and volumetric heat capacity. It is shown that, for the MCC powders, almost no changes in morphology or structural changes were observed during heating to temperatures up to 200 °C. An increase in relative density or temperature leads to a high thermal conductivity and the volumetric heat capacity. Among all MCC powders considered, Avicel DG showed the highest increase in thermal conductivity and the volumetric heat capacity, but this heat capacity was not sensitive to the measurement temperature. For lactose and mannitol, some endothermic events occurred during heating. The thermal conductivity increased with the increase in temperature and relative density. A model was also developed to describe the variation of the thermal conductivity and the volumetric heat capacity with the relative density and the temperature. It was shown that the empirical model can well predict the dependency of the thermal conductivity and the volumetric heat capacity on the relative density and the temperature.
The oral drug delivery system using bilayer (or multilayer) tablets has become more commonly used in therapeutic strategies. However, one of the most common problems associated with bilayer tablets is the insufficient interfacial strength between layers, which leads to product failure during manufacturing. Therefore, it is important to better understand the interfacial strength of bilayer pharmaceutical tablets. For this purpose, in this study, the interfacial strength of bilayer tablets made of microcrystalline cellulose (MCC PH 102) at various manufacturing conditions was systematically examined. Three cases were considered: (1) the effect of interfacial curvature on the interfacial strength, for which the interfaces between two layers with different curvatures were produced using flat, convex and concave punches. (2) The effect of water content on the interfacial strength, for which the powder was conditioned at various relative humidity before being used to produce bilayer tablets. (3) The effect of the particle size of the powder used in first layer on the interfacial strength, for which the feed powder was sieved to obtain powders with specific particle sizes that were then used to produce the first layer of the bilayer tablets. For all cases considered, direct tensile tests were performed to measure the tablet interfacial strength. It is found that the interfacial curvature, the water content and the particle size in the first layer affected the interfacial strength significantly. It is also shown that the tablet interfacial strength was increased when larger particles were used in the first layer, or when curved punches (i.e. either convex or concave punches) were used to produce curved interfaces with increased interfacial areas. In addition, a higher interfacial strength can also be achieved by properly controlling water content in the powder.
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.