Reactive Crystallization of Paracetamol in a Continuous Oscillatory Baffled Reactor

In this article, we report, for the first time, a reactive seeded cooling crystallization of paracetamol successfully performed in a continuous oscillatory baffled reactor (COBR). The synthesis of acetaminophen took place in the first part of the COBR and generated the solvent for crystallization via a specific ratio of starting materials. Seeded cooling crystallization was immediately commenced after the completion of the reaction in the second part of the COBR. We investigated the seeding strategy of three seed masses (10, 15, and 20 w/w%) at a fixed size in this work, enabling smooth and encrustation-free runs. We also estimated agglomeration by comparing the ideal to actual normalized product/seed sizes, which was confirmed by SEM images. The effect of mixing intensity on crystal properties was reported. Samples at two ports a known distance apart along the COBR enabled the study of steady states of the paracetamol concentration and crystal mean size in both temporal and spatial domains as well as the determination of the local and overall growth rates. Form I paracetamol particles were consistently produced with an average purity of 99.96%

A Comparative Evaluation of Hydrogenation of 3-Butyn-2-ol over Pd/Al₂O₃ in an Oscillatory Baffled Reactor and a Commercial Parr Reactor

A multiphase catalytic hydrogenation of 3-butyn-2-ol over Pd/Al₂O₃ to produce 3-buten-2-ol was for the first time investigated in both an oscillatory baffled reactor (OBR) and a commercial stirred tank reactor (Parr). Catalytic control was first identified in the Parr by evaluating the effects of mixing, initial molar ratio of 3-butyn-2-ol/Pd, and temperature on reaction rate. These conditions were then used as the benchmark for a comparable evaluation of the OBR in terms of reactor efficiency (power consumption) and hydrogen utilization (H₂ efficiency). Our systematic investigations demonstrate that, due to the enhanced mass transfer in the OBR, it consumes 5 times less power to achieve the same reaction rate and delivers 2.3 times higher H₂ efficiency and 50% less reaction time in comparison to the Parr

Characterization and modelling of antisolvent crystallization of salicylic acid in a continuous oscillatory baffled crystallizer

Using antisolvent crystallisation of salicylic acid as the model process, we report our experimental investigation into the temporal and spatial steady states of solution concentration and mean crystal size in a continuous oscillatory baffled crystallizer. The evolutions of the two parameters over time and distance along the crystallizer are measured for a variety of operating conditions. The results show that the attainment of long term temporal and spatial stabilities (>100 residence times) for the solute concentrations are easily achieved, whereas the temporal steady states of the mean crystal size are more difficult to accomplish, even though the spatial steady states have been obtained. A simplified population balance model is applied to the experimental data for the determination of nucleation and growth kinetic parameters. From which both the solution concentration and the mean size were predicted and matched to experimental values reasonably well. In addition, we have identified and executed the conditions of long term steady states for extended operation of 6.25. h to produce close to 1. kg of crystal product with minimal variation in crystal size (±3.01. μm)

Material characterisation and parameter effects on bulk solid dissolution rate of paracetamol in a stirred tank vessel using an in situ UV-ATR probe

The progress from batch to continuous manufacture of pharmaceuticals has highlighted the requirement for dosing solid feed material directly, efficiently and accurately into continuous flow systems. Solids are currently dissolved in batch vessels before feeding into a flow system. This study focuses on gaining scientific understanding on rate kinetics of solid dissolution and parameters affecting solid dosing in current batch systems as a starting point; the knowledge gained will inform future continuous solid dosing work. Paracetamol was the model compound and the mixtures of water/ IPA the solvent systems. An in situ UV spectrometer was used to quantify the concentration of solute in solution during dissolution. In this paper, we present the dissolution kinetics results from a parametric study of effects of temperature, solvents, mixing and particle sizes on dissolution characteristics in a stirred tank vessel. The dissolution profiles from our system are similar to that of published work, with the fastest kinetics for the micronised particles, albeit problematic when dosing as a single shot. Dissolution rate is increased with increasing temperature, solvent content (solubility), mixing intensity and decreasing particle siz

ASTROD and ASTROD I -- Overview and Progress

In this paper, we present an overview of ASTROD (Astrodynamical Space Test of Relativity using Optical Devices) and ASTROD I mission concepts and studies. The missions employ deep-space laser ranging using drag-free spacecraft to map the gravitational field in the solar-system. The solar-system gravitational field is determined by three factors: the dynamic distribution of matter in the solar system; the dynamic distribution of matter outside the solar system (galactic, cosmological, etc.) and gravitational waves propagating through the solar system. Different relativistic theories of gravity make different predictions of the solar-system gravitational field. Hence, precise measurements of the solar-system gravitational field test all these. The tests and observations include: (i) a precise determination of the relativistic parameters beta and gamma with 3-5 orders of magnitude improvement over previous measurements; (ii) a 1-2 order of magnitude improvement in the measurement of G-dot; (iii) a precise determination of any anomalous, constant acceleration Aa directed towards the Sun; (iv) a measurement of solar angular momentum via the Lense-Thirring effect; (v) the detection of solar g-mode oscillations via their changing gravity field, thus, providing a new eye to see inside the Sun; (vi) precise determination of the planetary orbit elements and masses; (viii) better determination of the orbits and masses of major asteroids; (ix) detection and observation of gravitational waves from massive black holes and galactic binary stars in the frequency range 0.05 mHz to 5 mHz; and (x) exploring background gravitational-waves.Comment: 17 pages, 6 figures, presented to The Third International ASTROD Symposium on Laser Astrodynamics, Space Test of Relativity and Gravitational-Wave Astronomy, Beijing, July 14-16, 2006; International Journal of Modern Physics D, in press (2008

An enhanced block validation framework with efficient consensus for secure consortium blockchains

Consortium blockchains have attracted considerable interest from academia and industry due to their low-cost installation and maintenance. However, typical consortium blockchains can be easily attacked by colluding block validators because of the limited number of miners in the systems. To address this problem, in this paper, we propose a novel block validation framework to enhance blockchain security. In the framework, the block validations are assisted and implemented by various lightweight nodes, e.g., edge devices, in addition to the typical blockchain miners. This improves the blockchain security but can cause an increased block validation delay and, thereby, reduced blockchain throughput. To tackle this challenge, we propose an effective method to select lightweight nodes based on their computing powers to maximize the blockchain throughput, and prove the uniqueness of the optimal nodes selection strategy. Security analysis and simulation results from the deployed consortium blockchain platform show that the proposed framework achieves higher throughput and security than the existing consortium blockchain models