Webinar: Powder Hydration Process in the Pharmaceutical Industry

Watch our Webinar: Powder Hydration Process in the Pharmaceutical Industry

In this webinar, ILC Dover Senior Field Application Specialist Jean-Marc Hanna discusses a method of transferring powders in a safe manner based on real user requirement specifications from a pharmaceutical site. It covers the design of a full powder hydration solution that enables the fast and safe transfer of several types of powders into a liquid phase, mixing powder of different properties into liquid.

Through an in-depth review of the problems inherent in transferring powders for the pharmaceutical industry, this webinar examines powder potency and operator protection, powder flow and hygroscopic behavior, technical solutions for delumping and mixing, cross contamination, and ergonomics.

Transcript

[Jean-Marc Hanna] 0:07 – Hello everyone and welcome. Thank you for joining this webinar today on the topic of powder hydration in the pharmaceutical industry. My name is Jean-Marc Hanna, and I’m a Senior Field Application Specialist at ILC Dover. I’m specialized in aerosol science, containment and contamination transfer, and I’m based in Switzerland. Now, let’s start the webinar.

WHAT PROBLEMS ARE WE SOLVING WITH THE RIGHT SOLUTION?

[Jean-Marc Hanna] 0:49 – What are the problems, and what are we looking to achieve when powder transfer is involved? Many factors have to be considered: weight, powder flow, humidity, chemical properties, product stability, risk and safety assessment, and delivery efficiency.

1:13 – Powder can create compact and agglomerated blocks, and powder behavior is never standard, like kitchen salt or cooking flour. We will show you how ILC Dover handles these challenges and the expertise we bring to achieve these objectives. Now, let’s turn to the topic of the day in more detail.

PHARMACEUTICAL PROCESS

[Jean-Marc Hanna] 1:41 – Today’s presentation focuses on the pharmaceutical workflow in chemical synthesis. We are considering production processes, including the arrival of raw products, sampling and weighing the required quantities of powder, and further transformations, from offloading powders into drums to offloading FIBCs into tanks. FIBCs are flexible intermediate bulk containers, and these operations might involve handling potent products with low OEL and high levels of concern.

2:32 – We will focus on the step that involves mixing a powder with a solvent, usually water or sometimes other liquids. This step occurs in a hydration tank and is part of an overall production process leading to the oral solid form of a pharmaceutical drug. The following workflow illustrates different possible stages of production. We can draw a parallel with the biopharmaceutical workflow where the media preparation step also involves mixing powders in a liquid to obtain a perfect mixture. Now, let’s talk about the main challenges of powder hydration.

FUNDAMENTAL CHALLENGE: GETTING POWDER INTO A MIX TANK

[Jean-Marc Hanna] 3:28 – When you’ve faced these challenges, you’ll say we need to provide a solution to deliver powder into a hydration tank and facilitate the mixing process. It looks simple on paper, but tanks can have various sizes because required quantities vary with batch sizes.

TYPICAL HYDRATION SYSTEM

[Jean-Marc Hanna] 3:52 – Required quantities are increasing, and handling powders in a safe and efficient manner is fundamental. Let’s talk about methods to deliver the powder into the tank and mix it with water.

4:20 – Let’s start with the manual charging method. Manual charging has multiple disadvantages and risks, such as operator exposure to powder-generated aerosols, contamination of the internal sides of the vessel, and lack of efficiency for powder mixing because a big lump of powder is dropped on one side of the hydration tank. Even if you think otherwise, this method is still widely used in pharmaceutical processes. Additionally, manual charging brings safety issues for the operator, such as the risk of falling or other catastrophic events, like spilling a bag’s contents in the room when it bursts after a fall. Protection of the operators is mandatory with individual protective equipment, and this method raises all red flags for operator health and safety if you consider containment and protection of operators.

5:34 – When containment is limited to paper or directly protective individual suits for an operator, you have missed something. Now, let’s think about operational ergonomics.

CONGESTED TANK TOP HEADS

[Jean-Marc Hanna] 5:53 – Ergonomics is not only about powder handling but also about the practicality of the workstation to accomplish the task. Bad posture has consequences, and if we think again about the fundamental challenge, why use a ladder, steps, or stairs? Why does an operator have to carry powder? What functions should we perform to reach the goal? Let’s jump to the next method with IBCs and FIBCs.

IMPROVES SAFETY

[Jean-Marc Hanna] 6:25 – IBCs (Intermediate Bulk Containers) bring some improvements as they need to be used with a lift, removing the health and safety issues. FIBCs (Flexible Intermediate Bulk Containers) and single-use bags provide an additional advantage by avoiding cleaning operations. The delivery speed of the powder is improved, but some powders with bad flow properties still create difficulties because of their hygroscopic behavior, requiring additional support equipment to help with delivery.

7:03 – For instance, sodium dihydrogen phosphate becomes like concrete when just drops of water are spread onto the powder. Another issue with this system is the butterfly valve, which creates a limitation in the aperture for powder delivery.

7:39 – Let’s speak about the next method: dense phase pneumatics transfer. As long as it works, it’s a good system. It’s an old system seen worldwide. But when it’s not working, it consumes labor and hours in maintenance due to clogged filters, powder valves blocked by fine dust, and the need for cleaning the distribution line. It requires height above the tank, and the vacuum pump installed in a technical area consumes high energy. Even if it’s semi-automated, it doesn’t improve what FIBCs provide in terms of performance.

8:35 – Considering the bigger picture, why do we deliver the powder alone on top of the vessel? Is there a better way to dispense the powder to mix it with liquid? Why not use the liquid as a carrier medium? This brings us to the next method, the rotor-stator device.

AVAILABLE METHODS

[Jean-Marc Hanna] 9:01 – This method is interesting for mixing because it enables the destruction of small clumps and mixes the powder with liquid to carry the mixture to the tank. However, one disadvantage is the increase in product temperature by the shearing forces imposed. Another issue is the complexity of cleaning this equipment.

9:37 – There is a better method providing considerable improvement: the JetMixer™. The JetMixer offers a powder-into-liquid delivery system with mixing capability. It is a one-step powder-into-liquid addition with efficient turbulent mixing. The JetMixer uses the Venturi effect to help mix the powder with liquid, enabling a perfect powder-liquid mixture.

10:07 – The injection system consists of an inlet pipe, the injection chamber, an outlet pipe, and a connection for the powder inlet. As there are no moving parts, the JetMixer is suitable for ATEX applications and explosive environments. It can be installed remotely, and the addition of a second pump enables the powder to be discharged from several containers. Pressure is measured before and after the mixing chamber, and a pressure sensor in the chamber allows the whole mixing process to be monitored.

11:01 – Let’s see an example of an application design where the JetMixer stands on a trolley. The system requires a connection to the power supply, compressed air, and the water line. Operators manually empty bags into a powder-feeding hopper. Another design shows a powder-feeding valve fitting between the hopper and the jet mixer at the bottom, which is hidden. For powders with good flow specifications, a cleaning-in-place system rinses the hopper and inside of the equipment to switch to another powder. These units are flexible and can be used in various applications, like connecting to several vessels. The operator can transfer different quantities of powder into several containers with the same unit.

13:02 – The equipment design must be suitable for the quantities delivered, with several sizes for the JetMixer and the hopper available. Now, let’s discuss a real case study of a powder hydration realization.

CASE STUDY – MID SCALE UNIT FOR BAGS/ FEATURES

[Jean-Marc Hanna] 13:28 – This case study involves handling powders with various flow specifications and solubility properties, proposing a perfect mixing of powder and water without operator action, avoiding operator exposure to fine dust, preventing powder bridging before mixing with liquid, determining the mass of powder remaining in the process, and avoiding cross-contamination. The system design consists of four main pieces of equipment, compliant with ATEX requirements and conditions, which are not very demanding.

PROCESS STEPS

[Jean-Marc Hanna] 14:31 – The process includes several steps. The three sequences in blue and orange involve operators, and the four processes are included in those diagrams. The final cleaning cycle resets the system for new powder delivery.

ADDITIONAL FUNCTIONALITIES

[Jean-Marc Hanna] 15:06 – Additional functionalities protect the operator from fine dust, weigh the powder dispensed into water, and clean the equipment for a new batch. The final P&ID (process and instrumentation diagram) includes all these features.

HOPPER

[Jean-Marc Hanna] 15:40 The first step is the hopper, where the operator acts after registering the batch. The grid at the bottom of the hopper may or may not be present, depending on whether the next step, lumping, is needed.

DELUMPING

[Jean-Marc Hanna] 16:17 – The JetBreaker™, a patented equipment, enables efficient and reliable powder delumping. Delivered from bags, powder can sometimes form blocks. This equipment suits any powder flow or chemical properties, reducing single blocks of up to 50 cm to a few millimeter grains in one step. The lump breaker grid is available in different sizes.

17:43 – Here’s a movie showing a JetBreaker in operation, with an asymmetric chamber where the rotor forces the product through comb teeth. If the grinding torque is too great, the gear motor stops and restarts in the opposite direction. Maximum torque is detected by measuring the current consumed. The rotation can be inverted manually or automatically.

18:43 – After using the JetBreaker, the powder grains are collected for the next step: the powder feeding valve.

DISPENSING

[Jean-Marc Hanna] 19:00 – The powder feeding valve works like a water mill wheel, calibrated for the powder’s solubility properties to deliver the right quantity into the JetMixer. Using a pneumatic actuator, it ensures efficient dispensing. Here’s another movie showing the powder valve’s rotation.

MIXING

[Jean-Marc Hanna] 19:53 – In the final step, the JetMixer, the water stream goes from upstream to downstream, mixing the powder directly into the stream and connecting to the hydration tank. The powder is completely mixed into the water during its journey through the pipes. This system includes a cleaning-in-place system, ensuring no contamination between batches.

POWDER HYDRATION FINAL EXECUTION

[Jean-Marc Hanna] 21:16 – The final system has a platform with a tray at hip level, improving ergonomic operation. The platform is not mechanically connected to the system, allowing for weighing of the offloaded powder. ATEX constraints have been managed, ensuring safety and compliance.

22:08 – The system’s qualification includes SP airspeed at operator levels, preventing exposure to aerosols by sucking air through a dedusting unit and passing it through a HEPA filter before releasing it back into the atmosphere. The hopper’s CIP features enable internal surface cleaning and drying before a new operation.

ADDITIONAL EXAMPLES

[Jean-Marc Hanna] 23:22 – Other examples include a PI powder hydration station for biopharmaceutical applications, dedicated to an EZ BioPac offloading in a contained manner. EZ BioPac is ILC Dover’s single-use powder transfer system, containing known quantities of powder as a buffer. It is docked to a JetBreaker by a lifting system. After the JetBreaker’s action, the powder is dispensed to a powder feeding valve and then a JetMixer, resulting in a perfect powder-liquid mixture.

24:34 – Another example is a hybrid station with a manual offloading of bags under 25 kg and an EZ BioPac for larger quantities, up to 100 kg.

25:30 – The final example is a hydration station for large bags (FIBCs). This station works similarly to the previous one but is much taller. A massaging system safely offloads the powder container into an enclosure, docking it safely to prevent exposure. The JetBreaker receives large lumps, breaking them into smaller grains for the powder feeding valve and JetMixer.

26:54 – The FIBC is lifted by a hoist, and the massaging system breaks clumps for delivery into the JetBreaker. Load cells weigh the dispensed powder into the liquid with around 400-500 grams precision. The system includes a cleaning-in-place solution for all parts from docking to the JetMixer.

POWDER HYDRATION: WHAT ARE WE SOLVING?

[Jean-Marc Hanna] 28:19 – Thanks to ILC Dover’s expertise, these systems provide efficient powder mixing, ensure safety, and bring flexibility to suit any powder hydration application. For OEB4 or OEB5 risk assessments, we will assess what equipment or parts need containment. The final result of this powder hydration solution is that we make the operator’s life easier and enhance yield, automating the process of mixing powder with water.

29:20 – Thank you for listening to my presentation. I await your questions.

[Stephanie Arthurs] 29:26 – Thank you, Jean-Marc. At this time, we don’t have any questions, but please reach out to us through our website at ilcdover.com. Each attendee will receive a copy of the recording shortly. We appreciate your attendance. Hold on, it looks like we have a question.

[Stephanie Arthurs] 29:51 – The question is: What viscosity range can the system work for? We routinely use liquids of 500 to 1000.

[Jean-Marc Hanna] 30:04 – That’s a question I will not be able to answer right now. I need to ask one of my colleagues who is not available at the moment, but I will get back to you quickly about that.

[Stephanie Arthurs] 30:28 – Great, and we have another question: How to proceed when we have several solids to add to the reactor, but with very different amounts, like 1000 kg and then several at 2 kg?

[Jean-Marc Hanna] 30:34 – That’s another interesting question. It depends on how the product is carried before, whether it is in an IBC of 1000 kg or any other solution. If it’s an FIBC, we could use a small system, but obviously, we would need two separate solutions for different amounts. Injecting 1000 kg into water takes time, and the difference between a small amount and a large amount requires separate systems. It also depends on the product’s packaging and how you want to dock it to the hydration system. The behavior of the powder also matters. If the 1000 kg powder doesn’t flow well, we need solutions to break clumps and ensure smooth flow into the liquid. For smaller amounts, a single system suffices, but it might require containment or a small bag holding the system. If it’s the same tank, we need to assess which powder goes in first.

[Stephanie Arthurs] 32:24 – We have another question: On the big bag dispensing station, where is the separation between weighing and non-weighing equipment to ensure 400 to 500 gram accuracy?

[Jean-Marc Hanna] 32:30 – The load cells are located here, managing the bag. The separation between weighing and non-weighing equipment is here, ensuring a 400-500 gram accuracy. The vertical load cells handle the load and are designed for seismic risks, ensuring precise measurements.

[Stephanie Arthurs] 34:40 – If anyone has additional questions, we will reach out to ensure they are answered correctly. One more question: Have you considered a single-use or hybrid stainless steel SUV version for bioprocessing?

[Jean-Marc Hanna] 35:29 – No, we haven’t. We focus on flexible solutions and single-use systems due to their disposal convenience. Stainless steel single-use solutions are not aligned with our design philosophy. However, if you have specific requirements or contexts in mind, we would be pleased to discuss and provide an appropriate solution.

[Stephanie Arthurs] 37:38 – For any other questions, please visit our website at ilcdover.com. We appreciate your time today. Thank you, Jean-Marc.

[Jean-Marc Hanna] 37:51 – Thank you, everyone, for your presence. Thank you, bye.

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