A modified Kushner-Moore approach to characterising small-scale blender performance impact on tablet compaction.

Continuous Direct Compaction (CDC) has emerged as a promising route towards producing solid dosage forms while reducing material, development time and energy consumption. Understanding the response of powder processing unit operations, especially blenders, is crucial. There is a substantial body of work around how lubrication via batch blender operation affects tablet critical quality attributes such as hardness and tensile strength. But, aside from being batch operations, the design of these blenders is such that they operate with low-shear, low-intensity mixing at Froude number values significantly below 0.4 (Froude number Fr being the dimensionless ratio of inertial to gravitational forces). The present work explores the performance of a mini-blender which has a fundamentally different mode of operation (static vessel with rotating blades around a mixing shaft as opposed to rotating vessel with no mixing shaft). This difference allows a substantially wider operating range in terms of speed and shear (and Fr values). The present work evaluates how its performance compares to other blenders studied in the literature. Tablet compaction data from blends produced at various intensities and regimes of mixing in the mini-blender follow a common trajectory. Model equations from literature are suitably modified by inclusion of the Froude number Fr, but only for situations where the Froude number was sufficiently high (1 < Fr). The results suggest that although a similar lubrication extent plateau is eventually reached it is the intensity of mixing (i.e. captured using the Froude number as a surrogate) which is important for the lubrication dynamics in the mini-blender, next to the number of revolutions. The degree of fill or headspace, on the other hand, is only crucial to the performance of common batch blenders. Testing using alternative formulations shows the same common trend across mixing intensities, suggesting the validity of the approach to capture lubrication dynamics for this system.

Investigating the Role of the Catalyst within Resorcinol-Formaldehyde Gel Synthesis.

Resorcinol-formaldehyde (RF) gels are porous materials synthesized via a sol-gel reaction and subsequently dried, producing structures with high surface areas and low densities-properties that are highly attractive for use in various applications. The RF gel reaction takes place in the presence of a catalyst, either acidic or basic in nature, the concentration of which significantly impacts final gel properties. The full extent of the catalyst's role, however, has been subject to debate, with the general consensus within the field being that it is simply a pH-adjuster. The work presented here explores this theory, in addition to other theories postulated in the literature, through the synthesis and analysis of RF gels catalysed by mixtures of relevant compounds with varying concentrations. The relationship between catalyst concentration and initial solution pH is decoupled, and the individual roles of both the cation and the anion within the catalyst are investigated. The results presented here point towards the significance of the metal cation within the RF gel reaction, with similar structural properties observed for gels synthesized at constant Na+ concentrations, regardless of the initial solution pH. Furthermore, through the use of alternative cations and anions within catalyst compounds, the potential effects of ions on the stabilization of macromolecules in solution are explored, the results of which suggest a 'Hofmeister-like' series could be applicable within the catalysis of RF gel reactions.

Advancing Computational Analysis of Porous Materials-Modeling Three-Dimensional Gas Adsorption in Organic Gels.

Assessing the efficacy of specific porous materials for use in various applications has been a central focus for many experimental studies over the years, with a view to altering the material properties according to the desired characteristics. The application potential for one such class of nanoporous materials-organic resorcinol-formaldehyde (RF) gels-is of particular interest, due to their attractive and adjustable properties. In this work, we simulate adsorption analysis using lattice-based mean field theory, both in individual pores and within three-dimensional porous materials generated from a kinetic Monte Carlo cluster aggregation model. We investigate the impacts of varying pore size and geometry on the adsorptive behavior, with results agreeing with those previously postulated in the literature. The adsorption analysis is carried out for porous materials simulated with varying catalyst concentrations and solids contents, allowing their structural properties to be assessed from resulting isotherms and the adsorption and desorption processes visualized using density color maps. Isotherm analysis indicated that both low catalyst concentrations and low solids contents resulted in structures with open transport pores that were larger in width, while high catalyst concentrations and solids contents resulted in structures with bottleneck pores that were narrower. We present results from both the simulated isotherms and pore size analysis distributions, in addition to results from RF gels synthesized in the lab and analyzed experimentally, with significant similarities observed between the two. Not only do the results of this comparison validate the kinetic Monte Carlo model's ability to successfully capture the formation of RF gels under varying synthesis parameters, but they also show significant promise for the tailoring of material properties in an efficient and computationally inexpensive manner-something which would be pivotal in realizing their full application potential, and could be applied to other porous materials whose formation mechanism operates under similar principles.

Modelling Organic Gel Growth in Three Dimensions: Textural and Fractal Properties of Resorcinol-Formaldehyde Gels.

Tailoring the properties of porous organic materials, such as resorcinol-formaldehyde gels, for use in various applications has been a central focus for many studies in recent years. In order to achieve effective optimisation for each application, this work aims to assess the impact of the various synthesis parameters on the final textural properties of the gel. Here, the formation of porous organic gels is modelled using a three-dimensional lattice-based Monte Carlo simulation. We model growth from monomer species into the interconnected primary clusters of a gel, and account for varying catalyst concentration and solids content, two parameters proven to control gel properties in experimental work. In addition to analysing the textural properties of the simulated materials, we also explore their fractal properties through correlation dimension and Hurst exponent calculations. The correlation dimension shows that while fractal properties are not typically observed in scattering experiments, they are possible to achieve with sufficiently low solids content and catalyst concentration. Furthermore, fractal properties are also apparent from the analysis of the diffusion path of guest species through the gel's porous network. This model, therefore, provides insight into how porous organic gels can be manufactured with their textural and fractal properties computationally tailored according to the intended application.

Effect of S-triazine Ring Substitution on the Synthesis of Organic Resorcinol-Formaldehyde Xerogels.

Resorcinol (R) and formaldehyde (F) gel synthesis has been well-studied along with alternative reagents. We present the synthesis of formaldehyde-based xerogels using chemically similar s-triazine precursors, with comparison to traditional analogues. The substitution ranges from tri-hydroxyl to tri-amine, with an intermediate species, allowing changing chemistry to be investigated. Each molecule (X) offers different acid/base properties, known to influence gel formation, as well as differences in crosslinking potential. Varying X/F ratios were selected to recreate the stoichiometry used in RF systems, where one represented higher F to match the increased reaction sites of the additives. X/C ratios were selected to probe different catalyst (C) ratios, while working within the range likely to produce viable gels. Results obtained show little impact for ammeline as an additive due to its similarity to resorcinol (activation sites and pKa); while melamine and cyanuric acid show differing behavior depending on the level of addition. Low concentrations show melamine to have the most impact due to increased activation and competition for formaldehyde; while at high concentrations, cyanuric acid is shown to have the greatest impact as it creates a more acidic environment, which diminishes textural character, possibly attributable to larger clusters and/or weaker cross-linking of the system.

Effect of Aromatic Amines on the Properties of Formaldehyde-Based Xerogels.

This study investigates the synthesis of formaldehyde-based xerogels using alternative aromatic precursors, with comparison to traditional resorcinol-formaldehyde analogues, in order to alter the chemical composition of the resulting gels. By replacing resorcinol with aromatic amine molecules, i.e., ammeline, melamine and melem, each expected to undergo similar reactions with formaldehyde as the substituted species, we found that for all substituted gels, at low additive contents, the gel structure was compromised and non-porous materials were formed, as opposed to the most abundant monomers, and therefore, these additives seem to act as impurities at low levels. Working towards higher additive contents, melem monomers exhibited low solubility (~5%), even at elevated temperatures, thereby limiting the range to which melem could act as a substitute, while melamine could be incorporated up to ~40% under acidic conditions, with enhanced microporosity over this range. Pure gels were successfully synthesised from ammeline, but their performance was inferior to resorcinol-formaldehyde gels, while melamine-formaldehyde analogues required acidic reaction conditions but shrank considerably on sub-critical drying, adversely affecting the gel properties and demonstrating their lack of potential as sorbents. This demonstrates the potential for the inclusion of aminated aromatics within resorcinol-based gel systems, however, only as partial substitutes and not complete replacements.

Modelling the formation of porous organic gels - how structural properties depend on growth conditions.

There has been significant research interest invested into the study of the formation and properties of porous organic materials, due to their widespread applications. However, present models in the literature do not fully explain the observations made for these systems, therefore, this work presents a model developed to fully capture growth from the monomeric species present in the initial stages of the gelation composition. In this work, we employ a two-dimensional lattice-based kinetic Monte Carlo model to investigate how growth processes impact the structural properties of model gels. Experimentally, gel growth is primarily controlled through catalyst concentration, which determines the density of species that are activated for rapid growth, and solids concentration; our model captures both of these dependencies. Increasing both solids content and percentage of activated monomers leads to a higher ratio of closed porosity, and higher values of accessible surface area with increasing level of activation. The generated structures are analysed for their fractal properties using a correlation dimension. Increasing both solids content and percentage of activated species leads to an increase in correlation dimension, which plateaus at a value of 2, independent of catalyst concentration, suggesting little structural change at high solid loadings, over 50%. The Hurst exponent of a random walker diffusing in the accessible pores shows the opposite trend, varying from ½ for unconstrained diffusion and reducing to ⅓ for diffusion through the pore network at the threshold of percolation. These characteristics support visual observations of increasing complexity and tortuosity of pore structures in the model cluster structures. The implications of these results, for the design of porous structures tailored to particular applications, are discussed.

Process Variable Optimization in the Manufacture of Resorcinol⁻Formaldehyde Gel Materials.

Influence of process parameters of resorcinol⁻formaldehyde xerogel manufacture on final gel structure was studied, including solids content, preparation/drying temperature, solvent exchange, and drying method. Xerogels produced using a range of solids content between 10 and 40 w/v% show improved textural character up to 30 w/v% with a subsequent decrease thereafter. Preparation/drying temperature shows a minimal threshold temperature of 55 °C is required to obtain a viable gel structure, with minimal impact on gel properties for further thermal increase. Improving the solvent exchange method by splitting the same amount of acetone used in this phase over the period of solvent exchange, rather than in a single application, shows an increase in total pore volume and average pore diameter, suggesting less shrinkage occurs during drying when using the improved method. Finally, comparing samples dried under vacuum and at ambient pressure, there seems to be less shrinkage when using vacuum drying compared to ambient drying, but these changes are insubstantial. Therefore, of the process parameters investigated, improved solvent exchange seems the most significant, and it is recommended that, economically, gels are produced using a solids content of 20 w/v% at a minimum temperature of 55 °C, with regular solvent replenishment in the exchange step, followed by ambient drying.