Articles

Application Note: Data for safe scale-up of a heterogeneous liquid phase reaction

The calorimetry (heat output) information provides a convenient means of monitoring the progress of the reaction. Combined with a simple visual observation of mixing it has enabled the process problem to be quickly identified and a solution to be tested.

Application Note: Evaluation of increase in throughput using a catalyst

A test of the effectiveness of an acid catalyst in reducing the batch time of an esterification reaction and whether the cooling system on a full scale reactor would be able to cope with the increased power output.

Application Note: Improvement in nitration process economics

Process optimistaion resulted in a significant increase in yield as well as simplified product work-up procedure, thus reducing the batch time in the process of nitration of an aromatic substrate.

Application Note: Investigation of plant crytallisation problem using an automated lab reactor

Looking at an existing process which invloved the crystallisation of an active pharmaceutical for an organic medium, precise control and recording of reactor and oil jacket temperature, plus stirrer speed enabled the study of the following: - Solubility curve, for different solvent purities - Systematic (factorial) study of several process variables and their influence on crystal shape and form.

Application Note: Method development for a crysatallisation step

The use of computer control rapidly produced substantial improvements in the commercial viability of a process. This greatly improved the crystallisation step in the case of a product that previously took nearly a week to filter, wash and dry, thus dominating the production cycle.

Application Note: Protection of dryer in the event of product composition

Adiabatic calorimetry in the Phi-TEC II shows that the product that needs drying before transportation will begin to decompose signficantly at around 100 degrees C (around 85 degrees C lower than quoted in the literature).

Application Note: The Development of Solubility and Metastability Design Spaces

UCD Crystallization Research Group found that the HEL polyblock turbidity screening device, when combined with polythermal methods, enhances process understanding and enhances quality by design (QbD). By gaining a understanding of the limitations and benefits of a solubility and metastability design space a suitable crystallization technique can be designed.

Application Note: The use of statistical experimental design in process optimization

This application note describes a case study completed by HEL to demonstrate how a straightforward experimental design approach and a miniature computer controlled multiple reactor system can be used to reduce the manufacturing costs of a commercial chemical process. The process investigated was the pilot plant scale manufacture of 1,3,5-triphenylbenzene.

Automated Measurement of Metastable Zones for Pharmaceutical Compounds

The automated laboratory reactor combined with turbidity meter method was used successfully to measure the metastable zone for a pharmaceutical intermediate, thus providing useful information to aid the development of the crystallization process for that compound.

Breakthroughs in on-line process particle sizing

Recent designs of laser reflection probes can be described as " process microscopes " because they now can report the true size of particles on-line and do this over a wide range of sizes, fully integrated into process equipment.

Crystallisation Tools for the Research Chemist

It is clear that crystallisation studies in parallel can be performed at sample sizes as low as 1ml or as large as several hundred millilitres. The data scales up reliably and thus provides an excellent early insight into the key variables. This article expands the functionality and applications of CrystalSCAN and Crystal Eyes from HEL.

Design of a miniature stirred bioreactor system for parallel microbial fermentation

The establishment of a high productivity microbial fermentation process requires the experimental investigation of many interacting variables. In order to speed up this procedure a novel miniature stirred bioreactor system is described which enables parallel operation of 4 - 16 independently controlled fermentations.

Development of hydrogenation reaction using parallel processing

Heterogeneous hydrogenation reactions can be performed in parallel and quantitative data can be generated in real time as the reaction proceeds. This is an important component of parallel processes development as it allows rapid evaluation of the results. Equally important, it has been shown that with well designed and fully instrumented reactors, performance at different scales varying by two orders of magnitude can be directly compared. This shows that for the three systems studied (HP Chemscan, HP auto-MATE and SIMULAR) the data is perfectly consistent.

Exothermicity Characteristics of Wolf Lake Heavy Oil, Athabasca Tar Sand and Medium Heavy Clair Oil

High pressure accelerating rate calorimetry (ARC) tests - using HEL's Phi-TEC II adiabatic calorimeter - have been performed on three different crude oils, at their respective reservoirs pressures. The experiments on medium heavy Clair oil and heavy Wolf Lake oil used clean silica sand, incorporating 3% kaolinite, to represent the reservoir matrix, whereas Athabasca Tar Sand was used in its preserved, virgin state.

Monitoring & feedback control of supersaturation using ATR-FTIR to produce an API

Automation, in-situ monitoring and process control tools are implemented to understand and control the crystallization of an active pharmaceutical ingredient in development.

Rapid Process Development and Scale-Up Using A Multiple Reactor System

This article presents case studies that show how computer control involving parallel synthesis in specially designed reactors, particularly on the 25-100 mL scale, can provide significant benefits to the development cycle of new synthetic compounds of commercial interest. By employing a combination of calorimetry data and other analytical measurements, it has been demonstrated that small-scale experimentation can produce data that is both representative and scaleable.

Runaway reaction hazard and venting of cyanide reaction

The runaway reaction hazard of a cyanide reaction initiated by an amine and caustic has been studied extensively and a venting strategy formulated from the data. The relief size necessary to safely relieve such a reaction has been calculated using thermal runaway data for a number of different situations, allowing for two-phase flow.

The Design of Safe Chemical Processes

A typical process in the pharmaceutical and related industries consists of a number of sequential steps where a range of carefully selected compounds are allowed to react in order to produce the required product or intermediate. In many cases, the reactions involved are exothermic, and therefore require cooling and careful process control in order to ensure safe operation. In addition, some of the raw materials or products may be unstable and have a tendency to thermally explode under certain operating conditions.

Thermal profiling for parallel on-line monitoring of biomass growth in miniature stirred bioreactors

The combination of a parallel miniature bioreactor system with a noninvasive on-line technique for estimation of culture kinetic parameters provides a valuable approach for the rapid optimisation of microbial fermentation processes. Here we report on the use of thermal profiling techniques for parallel online monitoring of cell growth in these bioreactors based on the natural heat generated by microbial culture.