Microdosing ingredients
Four factors determine the best solutions for microdosing:
- The active pharmaceutical ingredients (APIs) and/or excipients you’re handling;
- The intended use of the process—for R&D only or for R&D that will lead to production;
- The required levels of accuracy and repeatability; and
- Area constraints for both the R&D and the production processes.
APIs and excipients
Material costs are always key when microdosing pharmaceutical ingredients:
- How many ingredients does the tablet or capsule require? Each dosing unit may require a special design to accommodate the material’s specific characteristics and throughput requirements.
- What are the limitations of the dosing systems? Some low-percentage ingredients may require preblending to reduce costs and improve content accuracy. You will typically need to test individual or pre blended materials to design the dosing unit specifically for the application. If you can’t use the actual pharmaceutical ingredients for testing, you’ll need to use placebos. Orbetron can help you understand these limitations.
- What type of transfer system will refill the dosing units, and what are the material discharge requirements? Transfer can be challenging because some materials require special handling to prevent contamination or because the mechanical or vacuum transfer-system design may be large and difficult to use in connection with low-rate dosing equipment. Material discharge is important due to the need to contain some materials. Very fine particles can remain airborne for extended periods of time after discharge, and some materials can build up static over time when discharged at low rates.
R&D applications
R&D applications require numerous changeovers, short runs, and easy feeder removal and cleaning. For applications that are strictly R&D, dosing units must be very flexible and capable of feeding as many different pharmaceutical ingredients as possible. However, differences between ingredients can influence feeding performance, from throughput to material flow.
When moving from R&D to production scale, you will typically need larger dosing units, and the units may require control changes. Additional material testing may be necessary to accommodate your process needs, and some materials may not be suitable for feeding because of their flowability.
Orbetron, can assistance in material testing and designing a feeder capable of achieving the entire feed-rate range your application requires.
Accuracy and repeatability
Once you have developed your APIs and excipients and determined the percentage of each that your product requires, and identifying the necessary accuracy and repeatability for each dosing unit. We need to understand the type of process that is required. For batch-weighing processes, the information you have determined for each material, can provide the information needed to allow the dosing unit to operate in a coarse-dribble manner, in which the unit feeds most of the ingredient for the batch quickly in coarse mode and then slows to dribble mode to accurately feed the final amount. This can help maintain the tight tolerances required for certain materials.
With the introduction of continuous pharmaceutical manufacturing and the new technology being developed around this concept, feeding your ingredients becomes more critical. You must establish time-based variations, which are defined as changes in material weight over an acceptable timetable that you establish through volumetric or gravimetric testing. You can consider performance of the dosing unit on a minute-to-minute basis over a 30-minute period, but based on your material’s characteristics, you may want to consider more frequent intervals, such as every 15 or 30 seconds, over a 30-minute period. Prior material testing with Orbetron, can help you decide the time consideration. During R&D, you may be able to use only volumetric feeding due to the low feed rates, but when you move to the higher feed rates required for continuous production, you must determine whether to use volumetric or gravimetric feeding technology.
For continuous processes, accuracy at low feed rates is very dependent on the material’s flowability. You must determine not only each ingredient’s accuracy requirements to ensure the drug product’s effectiveness but also the feed rate at which you need to achieve that accuracy.
Achieving 1 percent accuracy at 10 g/h is different from achieving 1 percent accuracy at 100 g/h. You should understand your dosing unit’s capabilities and limitations before specifying an ingredient’s accuracy requirements. If you can’t achieve sufficient accuracy feeding low-percentage ingredients individually, you may need to pre blend 2 or 3 low-percentage ingredients and feed them together.
Area constraintsSpace limitations in the lab and production plant can present challenges when designing a manufacturing process. Orbetron has been been working on designs to reduce the size of their feeding devices. Microdosing units the size of a coffee cup are now available that can help you feed multiple ingredients into a process while using a smaller production frame. When designing a system, review your available operating area with your feeder supplier to determine the best configuration for your feeding equipment.
Roger Hultquist is president and co-owner at Orbetron, Cumberland, RI. The company supplies technology that ensures consistent and repeatable feeding of dry bulk solid and liquid materials.
Published by: hhtps://tabletscapsules.com
By Roger Hulquist, Orbetron LLC
Perhaps now more than ever, processors are being driven by their customers to maintain extremely tight color tolerances, use only a very specific amount of additives, and comply with additional requirements such as documentation. This has given rise to new feeding technology that can deliver material at extremely low rates. While low-rate feeding itself is not new, processors previously had asked their material suppliers to carry the burden of putting these components together, putting colors and certain additives into a single pellet. But as product requirements change, processors want the flexibility to add minor ingredients separately in order to make short runs, reduce cost to be more competitive, and customize the product to fit their customers’ changing needs. A large part of this is being driven by the medical industry, which has made processors in both injection molding and extrusion look at new ways they can feed these minor ingredients at low rates and maintain consistency.
When considering equipment for low-rate feeding in your injection molding or extrusion process, understanding your material (whether pellets or powder) and how it should be fed into your process is crucial. By reviewing the points below, you can determine whether your material is capable of being fed at the desired low rates to ensure consistent and repeatable feeding.
For the purposes of this article, “micro feeding” is defined as dosing materials from 200 g/hr (0.44 lb/hr) down to 1 g/hr (0.0022 lb/hr). Many processors wonder why it is critical to understand the material when feeding at low rates. The simple answer is that your material varies in shapes and sizes, which can affect feeding accuracy and consistency.
Lets start by reviewing the material considerations and define some basic points. In most molding applications we feed pellets; in extrusion applications we can feed both pellets and powder.
WHAT IS YOUR MATERIAL TYPE?
Some general information to know about your material would be its bulk density (lb/ft3); flowability (free flowing, fairly free flowing, or poorly flowing); and particle size or sizes. Do you have an accuracy requirement for these properties, and can it be achieved?
In the case of pellets, look at the pellet shapes (square, round, flat, cylindrical, etc.). Consistency of the pellet size and shape is a very important factor to ensure repeatability of your feeder. Medical- grade materials generally tend to be the most consistent in terms of pellet size and shape, while lower-cost materials tend to have more fines and varied sizes of pellets. When considering low-rate feeding, processors should make sure their material supplier can supply both clean and consistent material sizes.
In the case of powdered materials, particle size and output volume are generally consistent. That said, the flowability of the material can have the greatest impact on accuracy. It is common practice for feeders that handle cohesive or poorly flowing material to incorporate flow aids to overcome material inconsistency. These flow aids can come in both mechanical and software-based solutions. These flow aids are typically defined during the supplier’s testing program.
When considering low-rate feeding, processors should make sure their material supplier can supply both clean and consistent material shapes and sizes.
WHAT IS YOUR MATERIAL FEED RATE?
Most processors define feed rates for additives as a percentage of the overall weight. Consider the example of a small-tonnage medical molding application feeding color to produce a translucent product. In this scenario, a shot size of 1.68 g with a color additive of 0.06 g was equal to three pellets. This example should make it crystal clear why it is so important to understand material inconsistency. If the variation of the pellet was too great, the molder could not hold product color consistently. Due to the translucency of the product, feeding two or four pellets would make a difference in the end product’s color shade. The output from the feeder had to be a consistent three pellets. Our lab testing did find some variations of pellet sizes in different batches of colors. After some feeding tests, we were able to overcome these minor variations with some feeder modifications and produce a product with consistent color.
Feeding materials at higher rates typically mitigates a number of inconsistencies that standard materials have. During testing of different batches of materials, feeding under 100 g/hr, we have found that small changes in pellet sizes can have a significant impact on the feeder output. Example: Feeding a cylindrical pellet using a hole size of 3/16 in. would feed two to three pellets into the process but using a 5/32-in. hole would feed one to three pellets.
The example above shows that weight is important to establish your basis, but the actual micro-feeder volume output design (feeding three pellets) will have a greater impact on your true product consistency at low rates. This is the major reason material consistency is so crucial for feeding low rates.
QUESTIONS ABOUT FEEDING?
Contact us at sales@orbetron.com
Feeding Into The Process
Once the material type, expected rate, and the process have been defined, you can now establish a building block for the feeder type that will feed into the process. Most low-rate applications are being fed into small-tonnage molding machines and small extruders of 0.75-in. to 2-in. diam.
Incorporation of the feeder into the extruder requires some general review and consideration. Testing has shown that feeding the pellet or powdered materials as close to the feedscrew as possible will provide the best results. Avoid feeding additives into the stream of virgin material, as this may result in delays in getting the color started into the process and result in possible dispersion inconsistencies.
An additional advantage of feeding the material as close to the extruder screw as possible is that this makes it easier to accomplish material changeovers with minimal downtime.
Testing has shown that feeding the pellet or powdered materials as close to the feedscrew as possible will provide the processor with the best results.
WHAT TYPE OF FEEDER SHOULD I USE?
When considering feeding at such low rates it is important to understand that precise volumetric feeding is required. Orbetron offers different types and options of feeders. We offer both gravimetric and volumetric versions. When considering a gravimetric type of feeder at these low rates, the measurement of weight loss can be difficult. You will have to evaluate the pros and cons of using gravimetric or volumetric systems.
Typically, when considering feeding below 150 g/hr, gravimetric control may not be feasible due to longer weight recording times. If considering powder feeding, it will be important to look at how it is sealed to prevent leaks. Orbetron disc feeders are designed to feed powder or pellets by exchanging out the feed section. This reduces your overall cost and eliminates having to buy 2 different feeders that may have different designs.
If considering automated loading, be sure the loader and feeder are compatible and will not interfere with the feeding accuracy. If considering a venturi type of loader, be aware that during the loading time, material can be lifted from the material hopper due to the small amount of material storage in micro feeders.
As the plastics industry pushes toward lower-rate feeding requirements, it will be important to confirm minimum and maximum feeding rates that can be achieved. Orbetron will conduct test of your material to confirm what is possible, and make recommendations as required.
Summary:
If you use both pellets and powders, processors need to understand their material characteristics, min & max feed rates, and flowability. Contact Orbetron and we will design the feeder to fit your processing needs.