Having the ability to identify the problem and then establish root cause is critical to success. Unfortunately many solutions prohibit functional changes that are the result of poorly written and overly restrictive procedures. We see it all the time, restrictive standard operating procedures (SOPs) that do not provide the leeway to allow the technical team to react properly. The result is a series of Band-Aid solutions as work arounds. The first step is to provide training high level and developed skilled team members, and step two is to produce robust procedures. Combining these two steps will provide the tools and flexibility needed to be reactive to variables in order to overcome defects and produce the highest quality tablets possible, batch after batch.
The question is never, “What is our action plan if we have tablet defects?” A well prepared team knows that variables with ingredients, processing procedures, equipment condition, punches and dies, tablet press setup, and the skill of the technician all must come together in order to properly, effectively, and efficiently solve the problems at hand.
There is no such thing as a perfect blend
A professional tablet making team knows that no two batches are identical, they can be close but they are never identical. Large batches and production campaigns reveal common variations of ingredients create an environment that requires flexibility and knowledge. Slight changes in particle size distribution, moisture content, morphology, and density equate to tablet quality variations. Execution of processing procedures during granulating, milling, and blending compound the ingredient have as much to do with the quality of the tablet as the tablet press and the press tooling—punches and dies. Products that are launched into production without proper vetting often fail because they are proven in against the elements that occur over time.
Unfortunately there is no such thing as a perfect homogenous blend of ingredients. Too many “fines”, or dusty particles affect tablet weight control, compressibility—hardness and thickness—ejection forces, disintegration and dissolution profiles. Slight moisture changes will change the cohesive nature of the ingredients resulting in tablet hardness fluctuations. Particle shape surface morphology and polarity relates directly to ingredient interaction, which relates directly to segregation and ultimately to content uniformity issues. The list goes on. If the blend is different the technicians must react to those changes.
Since no two blends are exactly the same this means that the tablet press must be adjusted in a reactive way. The problem is compounded when the expectation is to run with the same settings throughout an entire batch, and batch after batch, expecting the same results. Most products require constant adjustment and change over the time. Time, temperature, settling, wear, dust control, head pressure, handling, and heat generation can have long term impact that will not be seen in the developmental or small batch operation.
Be ready to make changes
Forming granules of blended ingredients requires an in-depth knowledge of wet or dry granulating processing steps to enhance quality and performance in tablet making. Validation ranges are essential to enable a technician the ability to identify and operate to maximize a granulations performance in order to achieve maximum production rates. The ingredient variable, processing steps create performance criteria that must be matched during compression within the pre-established ranges. In other words the reason for ranges is to provide the ability to react to ingredient and process variations to produce a tablet with consistent quality attributes.
A skilled manager knows his team cannot expect the product to run in an identical way each day. Trying to run the way we did yesterday only results in defects. Rather we must react to minute changes in the environment, machine setup, raw material fluctuations, and meet those changes by using the tablet press features in a reactive way to maximize performance of the tablet. Quality trumps productivity every time. Tablet press features such as punch penetration, feeder speeds, pre-compression, and turret rpm are tools to overcome these ingredient and process variables. Novice procedures create fixed requirements, which remove the ability to adjust these fundamental functions, which result in the inability to correct defects effectively.
Isolating and identifying the defect must come before root cause. There are many CAPA’s (corrective action preventive action) that simply miss this point. If a defect is weight related the reaction must be concentrated on those attributes, functions, and processes that impact weights and dose. The same could be said for compression—hardness and thickness—ejection, disintegration and dissolution. The tablet press is the messenger and there are far too many instances where we shoot the messenger. The tablet is the result of not only the function of the tablet press but all it is the result of all steps in the process from the time ingredients are made, chipped, stored, weighed, granulated, milled, blended, and then compressed.
Training develops skills. It is important to systematically eliminate potential root causes before they happen. This means punches and dies must be inspected, polished and cleaned. A skilled technician knows the punches and dies are precision instruments and must be handled as such. Most damage to punches and dies does not occur during operation, rather it occurs from poor handling. This is a common variable that is often overlooked. The investigation team looks to see if the punches and dies were inspected and at all of the criteria used to evaluate the tooling, but they never look at the tooling. The interesting thing about procedures is they rarely say “look” and “listen.” Talk to the pros and they do just that, they look and listen.
Life in manufacturing is all about set-up, operations, cleaning, inspections and maintenance. A tablet press can last for decades or if mistreated will not perform well ever. A tablet press is one of the most demanding and intricate machines used in manufacturing. A thorough knowledge of proper setup means that the parts and components where cleaned, inspected, and maintained so that they are ready to be setup and then permitted to operate. Yet, it is common to see machines stop moments after they startup because corrections must be made. Establish robust cleaning, maintenance, and setup is the avenue to optimization. A marathon runner might be able to perform for one event, but only a well-conditioned runner can recover quickly and turn right back around and run another marathon. Many companies strive to produce and have that big production month, but most suffer the consequences and few are able to produce at high levels batch after batch, month after month.
It is common to learn that technicians are not permitted to make changes to punch penetration, pre-compression, feeder speed, and turret rpm because of the procedure”. If the formula is “normal” it works, if it’s not and there is even the slightest change and there are problems the first thing everyone does is stop the press and polish the punches, and run to tech services to solve the issue. The statement is simply to allow the technician to use the machine adjustments to overcome the variables within the formulation to help the product perform. This involves skills and interactions within the team. This means they must be knowledgeable and professional in achieving performance. Yet, most companies have only one trick in their pocket and that is to go and find their go-to person when there is a problem. Without that person, life is a struggle.
When it comes to equipment performance it is critical to know and expect performance. Much like flying a plane, the prep-work is on the ground: inspect, repair, and make certain the equipment is fully functional before you take off. Give the team— technicians, set-up, cleaners, and maintenance—the tools needed to perform the job. Understand that the average production run may not make it to the end of the batch without cleaning, repairs, and or maintenance as a result of poor product performance, improper machine care and novice setup skills. It is far too common to see extensive damage to the press and tooling because it was not stopped when it should have been but rather allowed to run to the end of the batch in the name of production.
Solving a defect occurs one step at a time
Sticking, capping, hardness, delamination, and black spots—DVDs, or dark visual defects—are the most common but avoidable issues. They have a direct relationship to all the factors we have been discussing. One thing to do when trying to solve a problem at the tablet press is to slow it down. We need to know if problem is the powder, press, or the tooling. Common defects like sticking, capping, hardness, or delamination are revealed quickly if the machine is slowed down significantly. If the problem still exists we must start to work pragmatically thru each step, one step at a time. If the problems shows improvement by slowing the press down. Now we know it is likely performance can improve thru machine adjustments. If it is a weight control issue then our hotlist must be related to all of the machine functions related to weight control—lower punch length, proper fill cam selection, scraper blade and tail-over die condition and setup, punch penetration, pre-compression force and so on.
Solving a defect is working back up the path of the potential root causes, the challenge is in making certain that we are identifying the problem correctly. Capping is when the top of the tablet separates or wants to separate—forms a fault line—between the top cap of the tablet and the tablet band, or cylinder. However, many teams incorrectly identify capping when the bottom of the cap comes off the tablet. This is known as de-lamination. We would solve delamination in a different way then capping. By slowing the press we can help identify changes more quickly. Solving defects is challenging and it takes skills and knowledge of the operation. Take it one step at a time and keep challenging those variables that are likely causing the problem.
Michael Tousey is the technical director and founder of Techceuticals and has over 43 years of tablet making experience. Techceuticals provides services, risk assessment, problem solving, and support for pharmaceutical, nutritional, chemical, and many related tablet and capsule manufacturers. The Techceuticals solid dosage training facility with state-of-the-art equipment is dedicated to tablet and capsule manufacturing. The non-GMP lab and training center are all-in-one to provide a true hands-on experience for training and troubleshooting. For more info: Techceuticals Tel: 216-658-8038; www.techceuticals.com; firstname.lastname@example.org.