Enhancement of learning for engineering students through constructivist methods

In student feedback, many students expressed difficulty with the concepts being taught. There was a difficulty with quick, in-class retrieval of information. To facilitate transfer, understanding and retention of knowledge there needs to be prior knowledge in the long-term memory. In the case of complex engineering problems, the performance outputs are a function of many input variables. Airfoil design is a good example—the engineer needs to understand the dependence of performance parameters on the input conditions along with the physical phenomena. Visual representation is a powerful means of depicting cause and effect relationships. It can be reasoned by adding relational, interpretive visuals to a lesson, a higher level of learning will occur. In the proposed interactive program the student is given control of input variables and can see the influence these have on the primary aerodynamic concepts. It creates realistic configurations from complex theoretical calculations, facilitating the storage of information in the long-term memory. This when complemented with traditional teaching methods, allows the student to develop conceptual understanding. The programme was used in second year undergraduate engineering teaching and over a three-year period was monitored and improved. Students’ performance was used to assess the effectiveness of the learning technique, as was student module feedback. The average class size for courses investigated was 26 students. The students performed better using this approach. It generated a motivation for further enquiry in the students and created an enthusiasm for student–student and student–lecturer interaction. This agrees with the constructivist theories and how social psychology affects learnin

The effects of particle shape, orientation, and reynolds number on particle-wall collisions

Crystallisation is an important unit operation used in the production of Active Pharmaceutical Ingredients (APIs). Crystallisation is typically carried out using seed crystals in a process called secondary nucleation that allows for greater control of crystal quality attributes. The mechanism of secondary nucleation is still not well understood. Particle attrition is one proposed mechanism. This work examines the conditions under which particle-wall collisions occur. This is done through the simulation of free-moving particles in an impinging jet flow using an immersed-boundary lattice Boltzmann method (IB-LBM) CFD solver. Particle Reynolds numbers from 100 to 400 are examined. Particle shapes with aspect ratios from 1:1 to 8:1 are used to represent the crystal habits of APIs. Particles that start in their low-drag or high-drag orientation maintain this orientation on approach to the target surface. All other intermediate initial orientations examined cause particles to rotate toward and overshoot their high-drag form before adopting their high-drag form in proximity to the target surface. Particles in their low-drag form remain in their initial orientation due to the symmetry of the computational domain. In this orientation, a collision is most likely to occur, and the minimum critical Reynolds number at which a particle-wall collision will occur can be determined. This value is shown to increase with increasing particle frontal length. Pointed or rounded leading edges are shown to improve a particle’s ability to pierce the boundary layer adjacent to the target surface and reduce this value. In cases where a Reynolds number of 400 is insufficient to cause a particle-wall collision, the particles’ minimum distances from the target surface are reported. Using the minimum critical Reynolds number values obtained, the approach velocities required for particles to collide with a wall are shown to be larger than the impeller tip speeds typically used during crystallisation operations. This work provides for the first time the conditions under which particle-wall collisions occur for varying shape and orientation, their behaviour on approach, and the associated impact velocities.</p

Plasticity in zwitterionic drugs: the bending properties of pregabalin and gabapentin and their hydrates

The investigation of mechanical properties in molecular crystals is emerging as a novel area of interest in crystal engineering. Indeed, good mechanical properties are required to manufacture pharmaceutical and technologically relevant substances into usable products. In such endeavour, bendable single crystals help to correlate microscopic structure to macroscopic properties for potential design. The hydrate forms of two anticonvulsant zwitterionic drugs, Pregabalin and Gabapentin, are two examples of crystalline materials that show macroscopic plasticity. The direct comparison of these structures with those of their anhydrous counterparts, which are brittle, suggests that the presence of water is critical for plasticity. In contrast, structural features such as molecular packing and anisotropic distribution of strong and weak interactions seem less important

Particle size distribution reconstruction: the moment surface method

Numerical simulation of typical chemical engineering processes, such as crystallisation, liquid-liquid extraction, milling and other multi-phase operations in which exist discrete and continuous phases are highly computationally intensive problems. For this reason numerical techniques, such as the Method of Moments (MOM) and Quadrature Method of Moments (QMOM), are utilised to improve the computational efficiency of these simulations. The downside to these approaches is that the simulations only produce the moments of the Particle Size Distribution (PSD), with the actual distribution not preserved. Knowledge of the PSD is very important for many industrial unit operations, particularly in dynamic multi-phase flows in chemical engineering where the composition of the discrete phase(s) evolves in time or space. For example, control of the PSD in crystallisation operations may be required to ensure more efficient downstream operations such as filtration and clarification. Several methods for the reconstruction of a distribution from its respective moments are available in the literature. Typically these techniques are quite computationally expensive. The novel technique presented in this paper involves the pre-calculation of the moments of a pre-defined 2-parameter Probability Density Function (PDF) for a range of values of each parameter. This pre-calculation results in moment surfaces where the surfaces are a function of the two defining parameters. The intersection of constant moment contour lines (termed moment iso-lines) on these surfaces using simulation moment outputs results in the recovery of the defining parameters. Knowledge of the PDF and the total particle count or solids loading allows for the reconstruction of the full PSD. This technique proves to be very efficient which makes it ideal for the reconstruction of large numbers of distributions, for example in transient population balance models or model-based control algorithms, without the need for repeated application of optimisation algorithms

Simultaneous parameter estimation and optimisation of a seeded anti-solvent crystallisation

A population balance incorporating nucleation, growth and agglomeration, solved using quadrature method of moments was coupled with a parameter estimation procedure. The seeded anti-solvent crystallisation of Paracetamol from methanol and water was chosen as the model system. All parameters concerned were regressed from moments calculated using the measured square weighted chord length distribution (CLD) generated by the FBRM. The FBRM and the concentration data are utilised together to obtain experimental moments that reflect the mass of solids in the tank. Using the estimated kinetic parameters, the crystallization model was validated using an additional experiment with a new non linear addition rate. Experimental crystal size distributions measured by laser diffraction are compared to CSDs calculated by the model and found to be in good agreement. No such work exists in the literature using FBRM to model an anti-solvent system which considers agglomeration. Based on the kinetic parameters estimated using the above method, the solution to the optimal anti-solvent addition rate profiles was obtained by applying nonlinear constrained multi-objective free final time formulation optimization on the validated model. These profiles were experimentally tested and CSD were compared with experiments used in the parameter estimation procedure. A 73.3% reduction in batch time was achieved with little impact on the CSD. Analyses of the various conflictions are presented with the aid of a pareto optimal plot to provide the practitioner with increased flexibility

Thermodynamic properties of paracetamol impurities 4-nitrophenol and 4'-chloroacetanilide and the impact of such impurities on the crystallisation of paracetamol from solution

The impact of structurally-related additives and impurities on active pharmaceutical ingredients is an essential yet poorly understood area. This work describes the characterisation of temperature-dependent solid-liquid properties of 4-nitrophenol and 4′chloroacetanilide in four different alcohols and their effect as impurities on the crystallisation of paracetamol. The solubility of 4-nitrophenol appeared to be significantly higher than paracetamol whereas the solubility of 4′chloroacetanilide was lower than paracetamol. The solubility difference between the impurities could be rationalised based on their molecular structure and hydrogen bonding interactions. The solubility data was modelled using empirical and thermodynamic models. Recrystallisation of paracetamol from solutions containing the highly soluble 4-nitrophenol impurity resulted in small uniformly sized high purity paracetamol crystals whereas the presence of the poorly soluble 4′chloroacetanilide impurity induced the formation of large needle shaped crystals of paracetamol. These differences in crystallisation are a consequence of the solubility difference and the different functional groups of paracetamol and its impurities. Overall this study serves as fundamental information for the development of crystallisation approaches for the purification of paracetamol from its main impurities

The effects of supersaturation, temperature, agitation and seed surface area on secondary nucleation

This work details the estimation of the secondary nucleation kinetics of paracetamol in ethanol solutions for cooling crystallisation processes, by means of isothermal under-seeded batch experiments. A numerical model, incorporating the population balance equation and the method of moments, has been developed to describe the seeding process for a typical cooling crystallisation process, accounting for the primary and secondary nucleation and subsequent crystal growth. Primary nucleation and growth kinetics have been previously evaluated from induction time experiments, and isothermal seeded batch experiments, respectively, allowing the secondary nucleation rate to be evaluated for a wide range of experimental conditions. The experimental technique involved the utilisation of two in-situ Process Analytical Techniques (PAT), with an Focused Beam Reflectance Measurement (FBRM®) utilised to qualitatively indicate the occurrence of secondary nucleation and an Attenuated Total Reflectance - Fourier Transform Infrared (ATRFTIR) probe employed for the online monitoring of solute concentration. Initial Particle Size Distributions (PSD) were used in conjunction with desupersaturation profiles to determine the secondary nucleation rate as a function of supersaturation, temperature and crystal surface area. Furthermore, the effects of agitation rate on the secondary nucleation rate were also investigated. Experimental parameters were compared to the model simulation, with the accuracy of the estimated secondary nucleation kinetics validated by means of the final product PSD and solute concentration

Tailoring crystal size distributions for product performance, compaction of paracetamol

Paracetamol crystals often exhibit poor compressibility properties, which results in capping issues. The Particle Size Distribution (PSD) of paracetamol was engineered to improve the compressibility of paracetamol crystals. This was accomplished by growing paracetamol crystals in the presence of additives. The active pharmaceutical ingredient Phenacetin and impurity 4-chloroacetanalide were used to modify the crystal properties of paracetamol. In solution, the phenacetin or 4-chloroacetanalide molecules adsorb onto the paracetamol crystal faces selectively (110 or 011) and inhibit the further growth of the paracetamol crystal and consequently, the paracetamol crystal growth is reduced substantially. For controlling the PSD of crystal to improve the compressibility of paracetamol crystals, a set of cooling crystallization experiments in the presence of additive was designed. According to a statistical experimental design, the cooling rate was the most effective parameter. The PSD was reduced when paracetamol crystallized from the controlled crystallization in the presence of less than 3 mol% of both additives. These smaller particles increased almost fourfold the compressibility of paracetamol in comparison to the commercial material. Moreover, tablets were prepared for each formulation using a direct compaction method. The results illustrated that a higher tablet hardness of paracetamol was achieved by tailoring the paracetamol crystal size distribution. In addition, the tablet disintegration time was higher for the formulation increased hardness. Overall, this work presents the potential use of structurally similar compounds as additives to alter the mechanical properties of an API