<b>Genetic Variation and Human Disease: Principles and Evolutionary Approaches</b>. By K. M. Weiss. (Cambridge University Press, Cambridge, 1995.) £16.95

Smith, Malcolm T.

doi:10.1017/s002193209723511x

Cited by 4 publications

(7 citation statements)

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“…The dispersion model (eq ), where the reactor is seen as a continuous path, is used to study RTD in oscillatory baffled flow systems. This model is applied on a continuous reactor when Bodenstein number is the range of 1–100. ,− …”

Section: Methodsmentioning

confidence: 99%

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Establishment of a Continuous Sonocrystallization Process for Lactose in an Oscillatory Baffled Crystallizer

Siddique

Brown

Houson

et al. 2015

Org. Process Res. Dev.

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Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plugflow behavior with residence times of 1−5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (LMH), as well as reduced cycle time (4 h compared to the 13−20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g•h −1 for 12−16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale. 50 principle of OBC has been described elsewhere. 4,5 The basic 51 design comprises a tubular network containing periodically 52 spaced orifice baffles superimposed with oscillatory motion of a 53 fluid. Oscillatory flow mixing has been developed and 54 investigated as a process intensification technology to achieve 55 efficient and controlled mixing in tubular crystallizers. Unlike 56 conventional tubular crystallizers in which the mixing is caused 57 by the turbulent net flow, the mixing achieved in an OBC is 58 mainly obtained by fluid oscillations and thereby the residence 59 time distribution within the device can be adjusted by the 60 oscillatory conditions and net flow rate allowing longer 61 residence times in short reactors and hence is more suitable 62 for slower processes like crystallization. 7−12 Previous studies 63 have shown that processing in an OBC resulted a greater 64 regularity of crystal shape with fewer defects and better control 65 over the crystallization process. A recent review provides a 66 detailed description of OBCs for crystallization as well as 67 summarizing the relevant literature. 63 These are attributed to 68 the uniform mixing when compared to a batch stirred tank 69 system. 3 Batch to ...

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Section: Methodsmentioning

confidence: 99%

“…Most of the previous RTD studies were performed by standard imperfect pulse injection techniques in which the concentration time profile at the two points of the system was measured and an axial dispersion model was applied following statistical analysis of data …”

Section: Methodsmentioning

confidence: 99%

Establishment of a Continuous Sonocrystallization Process for Lactose in an Oscillatory Baffled Crystallizer

Siddique

Brown

Houson

et al. 2015

Org. Process Res. Dev.

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“…(iii) Selection and use of reagents to run the process safely at the production level, as plant safety is the most important concern always. Here this was achieved by the use of Vitride instead of LiAlH 4 and borane dimethylsulfide (BH 3 ·SMe 2 ). In some patents, NaBH 4 was also reported, but it was unfruitful in our study.…”

Section: Resultsmentioning

confidence: 99%

“…The reduction of the amide functionality of compound 4 was tested with NaBH 4 and DIBAL-H, but the reactions were not successful. A literature search revealed that Vitride (Red-Al), chemically known as sodium bis(2-methoxyethoxy)aluminum hydride, is the best option among the available reagents for reduction of both the amide to the amine and the ketone to the 2° alcohol in compound 4 at the production level because Vitride (i) does not have an inconvenient pyrophoric nature and short shelf life, (ii) reacts with air and moisture exothermically but does not ignite, (iii) tolerates higher temperatures, and (iv) is soluble in aromatic solvents. Interestingly, in one patent, the reduction of the amide and ketone functionalities in compound 4 using Vitride was reported .…”

Section: Resultsmentioning

confidence: 99%

Old is Gold? Nefopam Hydrochloride, a Non-opioid and Non-steroidal Analgesic Drug and Its Practical One-Pot Synthesis in a Single Solvent for Large-Scale Production

Mohan

Krishnaiah

Babu

et al. 2017

Org. Process Res. Dev.

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Nefopam hydrochloride is extensively used in most of the European countries until today as an analgesic because of its non-opiate (non-narcotic) and non-steroidal action with fewer side effects compared with opioid and other analgesics, which cause more troublesome side effects. A multikilogram synthesis of nefopam hydrochloride has been achieved in one pot using a single solvent (toluene). A ≥99.9% purity of the active pharmaceutical ingredient (API) was achieved in excellent overall yield (≥79%). The one-pot, five-step synthetic process involves formation of an acid chloride (3) from benzoylbenzoic acid (2) followed by amidation (4), reduction (5), cyclization (6), and formation of the hydrochloride salt (1). The major advantages include (i) use of a single solvent, (ii) >90% conversion in each step, (iii) a cost-effective and operationally friendly process, (iv) averting the formation of genotoxic impurities, and (v) improved overall yield (≥79%) provided by the one-pot operation. For the first time, we report the characterization data of API 1, intermediates 3, 4, and 5, and also a possible impurity (5a).

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“…12 In comparison to lithium aluminum hydride (LAH), SMEAH is much better soluble, easier to handle, insensitive to dry air, thermally stable (<205 °C), and non-violently reacting with water, which makes it an invaluable reducing agent for both laboratory and industrial use. 13 Although it has been documented that SMEAH exhibited a unique reactivity and selectivity in some cases, 13,14 we have been using it as an equivalent reagent to LAH for numerous amide reductions.…”

Section: Introductionmentioning

confidence: 99%

One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles

2020

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Genetic Variation and Human Disease: Principles and Evolutionary Approaches. By K. M. Weiss. (Cambridge University Press, Cambridge, 1995.) £16.95

Cited by 4 publications

References 0 publications

Establishment of a Continuous Sonocrystallization Process for Lactose in an Oscillatory Baffled Crystallizer

Establishment of a Continuous Sonocrystallization Process for Lactose in an Oscillatory Baffled Crystallizer

Old is Gold? Nefopam Hydrochloride, a Non-opioid and Non-steroidal Analgesic Drug and Its Practical One-Pot Synthesis in a Single Solvent for Large-Scale Production

One-pot method for the synthesis of 1-aryl-2-aminoalkanol derivatives from the corresponding amides or nitriles

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