Erwin Eekelder
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More and more companies in varying industries are trying to make the transition to low flow solutions. Especially in the chemical industry and food & pharma market the trend is to focus on continuous manufacturing, waste reduction, lower downtime and more flexibility. In these industries the availability of ultrasonic flow meters for liquids suitable for 1” pipe lines or larger are enormous, but it is much harder finding solutions for smaller line sizes. Conventional ultrasonic flow meters use either the Doppler Effect or Transit Time measurement. These techniques are practically suitable for large bore sizes.

But what about ultrasonic flow meters for flow rates lower than 1500 ml/min or even 200 ml/min?

Due to the complexity of physics and technology there are not many measurement principles present in this particular flow area, especially ultrasonic flow meters. Therefore the big challenge was to find a solution to use ultrasound in tubes with very small diameters. In close collaboration with TNO (Netherlands organization for applied scientific research) Bronkhorst managed to develop an innovative instrument using Ultrasonic Wave Technology. This technology is applied in the new ES-FLOW™ series for measuring liquid volume flows between 4 to 1500 ml/min independent of liquid density, temperature and viscosity with an accuracy of 1% of rate ± 1 ml/min.

How does Ultrasonic Wave Technology work?

The ES-FLOW™ is based on ultrasonic wave technology. Measuring is done in a straight stainless steel tube with an inner diameter of 1.3 mm, without obstructions or dead spaces. At the outer surface of the sensor tube multiple transducer discs are located which create ultrasonic waves by radially oscillation. Every transducer can send and receive, therefore all up- and down-stream combinations are recorded and processed. By accurately measuring the time difference between the recordings (nanosecond range) the flow velocity and speed of sound is calculated. Knowing these parameters and the exact tube crosssection, the ES-FLOW™ is able to measure liquid volume flows. The distinctive character of this flowmeter is that it’s capable to measure the actual speed of sound, meaning that the technology is liquid independent and calibration per fluid is not necessary. Next to that the speed of sound can be used as an indicator of the type of fluid present in the flowmeter.

transducer discs and sensor tube picture1: transducer discs and sensor tube  

Four reasons why to use the ES-FLOW™ Ultrasonic flow meter:

1. One sensor for multiple liquids

Many companies have changing process conditions and make use of various liquids like additives or solvents. As the ES-FLOW™ technology is fluid independent, recalibration is not needed with liquid changes. Also non-conductive liquids as demi water can be measured.

2. Easy to clean and reduced risk of clogging

Cleaning processes are often time consuming. Due to the straight sensor tube design with no dead volume, particles have reduced chance of clogging the instrument. Cleaning can be done in a few minutes therefore the amount of down time will be limited.

3.Vibration insensitive

Ultrasonic measurement is not sensitive for vibrations as it doesn’t rely on frequencies or rotations. It is also irrelevant if the flow is laminar or turbulent.

4. Integrated PID controller and fast response

The on-board PID controller can be used to drive a control valve or pump, enabling users to establish a complete, compact control loop with fast response time.

Anthony O'Keeffe
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Learn about our experience using a Coriolis mass flow controller as a solution in a continuous reactor used to produce pharmaceuticals.

My interest in the adoption of continuous manufacturing at pharmaceutical manufacturers was sparked by a customer who contacted us to support them with the exact dosing of pharmaceutical excipients. This customer was planning a continuous pharmaceutical manufacturing facility.

Batch process manufacturing

Traditionally, most human pharmaceuticals are manufactured in a step by step batch process with extensive tests between steps to insure consistent quality and efficacy of the finished medicine.

The manufacture of pharmaceuticals is a highly-regulated process with government agencies inspecting and approving both the process and the facilities where medicines are manufactured. In 2016 the US Food and Drug Administration (FDA) allowed for the first time in its history a manufacturer to switch from the traditional batch manufacturing process to a continuous manufacturing process

Continuous process manufacturing

Continuous manufacturing is a pioneering technology that has the potential to transform how medicines are made in the future. Improvements in Process Analytical Technology (PAT) has allowed the automation and streamlining of what were previous laborious step by step manufacturing processes. It is now possible to accurately mix ingredients in a continuous reactor, carefully monitor and control the reaction rate and achieve higher yields than what was feasible just 10 years ago.

The liquid flow rates in these new continuous process systems are much smaller than what was traditionally encountered in the older batch processes. Instead of tonnes per hour, typical plants operate at flows of kilogram per hour (kg/hr) and in some areas even grams per hour (g/hr) or volume flow ml/h.

When using Continuous Manufacturing?

New medicines tend to be targeted at niche illnesses and don’t require the large quantities of active pharmaceutical ingredients manufactured in the past. Continuous Pharmaceutical Manufacturing is an ideal solution to manufacture these new drugs.

Since Bronkhorst offer the most extensive product range of low flow mass- and volume flow meters and controllers on the market, we were selected by the customer and charged with finding the optimum flow monitoring and control solution for the new process.

Coriolis mass flow controllers bring the solution

The customer required a process that was flexible, capable of monitoring and controlling the flow of different fluids with an inbuilt ability to automatically adjust itself for any pressure variations or disruptions. Additionally the customer required extensive logging of real time flow data and control via their DCS control system.

After careful consideration of the process requirements, we recommended our mini CORI-FLOW mass flow controller combined with a gear pump as the ideal solution to the demanding flow control requirements of the Continuous Pharmaceutical Manufacturing process.

Skid with mass flow meters and controllers

The decisive factor to use the mini CORI-FLOW mass flow controller here were its characteristic features:

  • Direct mass flow measurement, independent of fluid properties
  • Capability to measure density and temperature
  • The ability to switch to volume flow
  • High accuracy, excellent repeatability
  • Compact design, with stand-alone integrated PID controller for fast and stable control
  • Suitable for a wide flow range
  • Digital technology allowing interface with DCS systems using Profibus
  • Chemically resistant stainless steel and hastelloy wetted parts
  • A closed control loop that allows a rapid response by controlling the pump directly to change process conditions
  • When coupled with our IN-PRESS pressure controller the system offers the flexibility of flow and pressure control for some critical parts of the process.
  • All parameters can be logged, therefore this technology offered excellent traceability of the process

Please download our flyer 'Continuous Pharmaceutical Manufacturing' for more information.