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Pharmaceutical tablets have been the most dominant form for drug delivery and they need to be strong enough to withstand external stresses due to packaging and loading conditions before use. The strength of the produced tablets, which is characterised by their compressibility and compactibility, is usually deter-mined through a physical prototype. This process is sometimes quite expensive and time consuming. Therefore, simulating this process before hand can over-come this problem. A technique for shape modelling of pharmaceutical tablets based on the use of Partial Differential Equations is presented in this thesis. The volume and the sur-face area of the generated parametric tablet in various shapes have been es-timated numerically. This work also presents an extended formulation of the PDE method to a higher dimensional space by increasing the number of pa-rameters responsible for describing the surface in order to generate a solid tab-let. The shape and size of the generated solid tablets can be changed by ex-ploiting the analytic expressions relating the coefficients associated with the PDE method. The solution of the axisymmetric boundary value problem for a finite cylinder subject to a uniform axial load has been utilised in order to model a displace-ment component of a compressed PDE-based representation of a flat-faced round tablet. The simulation results, which are analysed using the Heckel model, show that the developed model is capable of predicting the compressibility of pharmaceutical powders since it fits the experimental data accurately. The opti-mal design of pharmaceutical tablets with particular volume and maximum strength has been obtained using an automatic design optimisation which is performed by combining the PDE method and a standard method for numerical optimisation.

No / Pharmaceutical tablets have been the most dominant form for drug delivery and most of them are used in the oral administration of drugs. These tablets need to be strong enough so that they can tolerate external stresses. Hence, during the design process, it is important to produce tablets with maximum mechanical strength while conserving the properties of powder form components. The mechanical properties of these tablets are assessed by measuring the tensile strength, which is commonly measured using diametrical or axial compression tests. This work describes the parametric design and optimisation of solid pharmaceutical tablets in cylindrical and spherical shapes, which are obtained using a formulation based on the use of Partial Differential Equations (PDEs) for shape design. The PDE-based formulation is capable of parameterised complex shapes using the information from some boundary curves that describe the shape. It is shown that the optimal design of pharmaceutical tablets with a particular volume and maximum strength can be obtained using an automatic design optimisation which is performed by combining the PDE method and a standard method for numerical optimisation.

Pharmaceutical tablets have been the most dominant form for drug delivery and they need to be strong enough to withstand external stresses due to packaging and loading conditions before use. The strength of the produced tablets, which is characterised by their compressibility and compactibility, is usually deter-mined through a physical prototype. This process is sometimes quite expensive and time consuming. Therefore, simulating this process before hand can over-come this problem. A technique for shape modelling of pharmaceutical tablets based on the use of Partial Differential Equations is presented in this thesis. The volume and the sur-face area of the generated parametric tablet in various shapes have been es-timated numerically. This work also presents an extended formulation of the PDE method to a higher dimensional space by increasing the number of pa-rameters responsible for describing the surface in order to generate a solid tab-let. The shape and size of the generated solid tablets can be changed by ex-ploiting the analytic expressions relating the coefficients associated with the PDE method. The solution of the axisymmetric boundary value problem for a finite cylinder subject to a uniform axial load has been utilised in order to model a displace-ment component of a compressed PDE-based representation of a flat-faced round tablet. The simulation results, which are analysed using the Heckel model, show that the developed model is capable of predicting the compressibility of pharmaceutical powders since it fits the experimental data accurately. The opti-mal design of pharmaceutical tablets with particular volume and maximum strength has been obtained using an automatic design optimisation which is performed by combining the PDE method and a standard method for numerical optimisation.

This research project aimed to develop a condition monitoring system for the final production quality of pharmaceutical tablets and detection capping and lamination during powder compression process using the acoustic emission (AE) method. Pharmaceutical tablet manufacturers obliged by regulatory bodies to test the tablet's physical properties such as hardness, dissolution and disintegration before the tablets are released to the market. Most of the existing methods and techniques for testing and monitoring these tablet's properties are performed at the tablet post-compression stage. Furthermore, these tests are destructive in nature. Early experimental investigations revealed that the AE energy that is generated during powder compression is directly proportional to the peak force that is required to crush the tablet, i. e. crushing strength. Further laboratory and industrial experimental investigation have been conducted to study the relationship between the AE signals and the compression conditions. Traditional AE signal features such as energy, count, peak amplitude, average signal level, event duration and rise time were recorded. AE data analysis with the aid of advanced classification algorithm, fuzzy C-mean clustering showed that the AE energy is a very useful parameter in tablet condition monitoring. It was found that the AE energy that is generated during powder compression is sensitive to the process and is directly proportional to the compression speed, particle size, homogeneity of mixture and the amount of material present. Also this AE signal is dependent upon the type of material used as the tablet filler. Acoustic emission has been shown to be a useful technique for characterising some of the complex physical changes which occur during tabletting. Capping and lamination are serious problems that are encountered during tabletting. A capped or laminated tablet is one which no longer retains its mechanical integrity and exhibit low strength characteristics. Capping and lamination can be caused by a number of factors such as excessive pressure, insufficient binder in the granules and poor material flowabilities. However, capping and lamination can also occur randomly and they are also dependent upon the material used in tabletting. It was possible to identify a capped or laminated tablet by monitoring the AE energy level during continuous on-line monitoring of tabletting. Capped tablets indicated by low level of AE energy. The proposed condition monitoring system aimed to set the AE energy threshold that could discriminate between capped and non-capped tablets. This was based upon statistical distributions of the AE energy values for both the capped and non-capped tablets. The system aims to minimise the rate of false alarms (indication of capping when in reality capping has not occurred) and the rate of missed detection (an indication of non capping, when in reality capping has occurred). A novel approach that employs both the AE method and the receiver operating characteristic (ROC) curve was proposed for the on-line detection of capping and lamination during tabletting. The proposed system employs AE energy as the discriminating parameter to detect between capped and non-capped tablets. The ROC curve was constructed from the area under the two distributions of both capped and non-capped tablet. This curve shows a trade-off between the probabilities of true detection rate and false alarm rate for capped and non-capped tablet. A two-graph receiver operating characteristic (ROC) curve was presented as a modification of the original ROC curve to enable an operator to directly select the desired energy threshold for tablet monitoring. This plot shows the ROC co-ordinate as a function of the threshold value over the entire threshold (AE energy) range for all test outcomes. An alternative way of deciding a threshold based on the slope of the ROC curve was also developed. The slope of the ROC curve represents the optimal operating point on the curve. It depends upon the penalties cost of capping and the prevalence of capping. Sets of guidelines have been outlined for decision making i.e. threshold setting. These guidelines take into account both the prevalence of capping in manufacturing and the cost associated with various outcomes of tablet formation. The proposed condition monitoring system also relates AE monitoring to non-AE measurement as it enable an operator predicting tablet hardness and disintegration form the AE energy, a relationship which was established in this research.

Yes / Detailed design of pharmaceutical tablets is essential nowadays in order to produce robust tablets with tailor-made properties. Compressibility and compactibility are the main compaction properties involved in the design and development of solid dosage forms. The data obtained from measured forces and displacements of the punch are normally analysed using the Heckel model to assess the mechanical behaviour of pharmaceutical powders. In this paper, we present a technique for shape modelling of pharmaceutical tablets based on the PDE method. We extended the formulation of the PDE method to a higher dimensional space in order to generate a solid tablet and a cuboid mesh is created to represent the tablet’s components. We also modelled the displacement components of a compressed PDE-based representation of a tablet by utilising the solution of the axisymmetric boundary value problem for a finite cylinder subject to a uniform axial load. The experimental data and the results obtained from the developed model are shown in Heckel plots and a good agreement is found between both. / Available in full text since 5th Feb 2013 following the publisher's embargo period.

<p dir="ltr">We present a systematic approach for integrating reduced-order models of tableting with upstream pharmaceutical unit operations. This method identifies critical material attributes (CMAs) and process parameters (CPPs) from upstream operations, describing their coupling to both first and second orders, while selecting the appropriate mathematical forms and estimating parameters. The coupling is modeled using normalized bivariate rational functions.</p><p dir="ltr">The approach is demonstrated for dry granulation, a process that enhances powder flowability but compromises tabletability by reducing particle porosity and increasing plastic work. Using a formulation of 10\% w/w acetaminophen and 90\% w/w microcrystalline cellulose, granules with varying densities and size distributions are produced, and tablets of different relative densities are fabricated. This work provides essential insights for end-to-end process integration, control, and optimization of dry granulation and tableting. It also identifies granule properties that predominantly influence the four stages of powder compaction: die filling, compaction, unloading, and ejection.</p><p dir="ltr">Furthermore, we examine the effects of excipients such as lubricants (magnesium stearate) and glidants (silica) on tablet critical quality attributes (CQAs) in continuous manufacturing. Lubricants were found to affect all compaction stages, with sensitivity to mixing time, while glidants influenced bulk density and tensile strength without significantly impacting tablet density or compaction force. Reduced-order models are developed to predict tablet weight, density, and tensile strength based on excipient concentration and mixing time. These models are integral to implementing real-time control under the quality-by-control paradigm.</p>