Frederick J. Murray
President
KORSCH America Inc.
What challenges and trends are tablet compression operations (or processes) faced with today?
In general, there is an industry trend toward the need for increased capacity, efficiency, uptime, and utilization – and this trend is certainly prevalent in most tablet production environments. Increasing overall capacity with fewer machines and fewer operators is driving requirements for fast change strategies, which involve multiple turrets, multiple sets of change parts, and streamlined procedures. In addition, this trend requires process optimization to ensure that each product is running at the maximum validated speed, and with maximum possible yields. From an equipment perspective, this trend requires a higher level of flexibility, and a tablet press design that is extremely versatile, and able to produce the broadest range of tablet shapes, sizes, and formats on a single machine platform. KORSCH has addressed this need with an innovative machine design that can produce single-layer, bi-layer, tri-layer, and core-coated tablets on the same machine – using a series of simple conversion kits – to insure maximum machine utilization, efficiency, and uptime.
The major challenge associated with this trend toward higher capacity and efficiency is to ensure that the quality of the process is maintained at the highest level. The latest KORSCH designs are intended to meet this challenge by offering a faster and simpler changeover process, with minimal parts and quick disconnect solutions. The flexible platform allows the site to produce any new product, which is introduced through development or acquisition channels, without acquiring new or special machinery. From a controls perspective, the product recipe capability accelerates the batch start and minimizes start-up scrap. The press force control system and tablet rejection system (with verification) insure that the process remains under control, and the electronic audit trail documents (event log, alarm log, reject log) permit the highest level of batch documentation, and an effective tool to evaluate the efficiency of the tablet compression operation.
How can the tablet manufacturing processes be improved upon in the foreseeable future? Are there any practices that should be adopted in order to optimize the tablet press operation?
There are a variety of methods that can be used to improve tablet manufacturing operations. First, the integration of peripheral equipment (deduster, metal check, tablet tester, tablet collection system) to the tablet press control system offers a system approach which can drive efficiency. Second, the comprehensive batch data that is generated by the tablet press control system – event logs, alarm logs, reject logs, parameter trend reports – can all be used to evaluate and to identify improvement opportunities. An analysis of machine uptime in the context of the alarm log will identify the most critical alarms that are contributing to machine downtime. An analysis of the event log can identify opportunities for improved training to insure that machine adjustments are being made correctly and consistently across the operation. An analysis of the tablet reject log and batch yield data will permit an assessment of the machine set-up. In short –the data that is generated by the tablet press can be reviewed in an analytical way to develop an action plan to bring meaningful improvement to the operation.
With regard to recommended practices, it is important first to fully understand the current baselines, in terms of uptime, efficiency, average throughput, changeover time, and production yields. The next step is to identify the major opportunities for improvement which may entail process optimization (output, yield, tablet quality), changeover optimization (additional turret, change parts), training initiatives (setup, changeover, troubleshooting), and technology solutions (automated tablet testing, automated tablet collection).
Matt Hicks
COO
Federal Equipment
What challenges and trends are tablet compression operations (or processes) faced with today?
Product containment. As compounds become more difficult to handle because they are sensitive to the environment, sensitive to contact with other materials, or dangerous to tablet press operators, product and dust containment become more and more of a concern.
How can the tablet manufacturing processes be improved upon in the foreseeable future? Are there any practices that should be adopted in order to optimize the tablet press operation?
Tablet presses that are easy to clean and change-over will be key to the pharmaceutical industry’s future. As the pharmaceutical industry looks to contain costs with “lean manufacturing” and “six-sigma” concepts, equipment downtime for cleaning and change over becomes a critical metric.
Jośe Colón
Physical Testing Product Manager
Sotax
What challenges and trends do you see for solid oral dosage equipment (or production in general) faced with today?
Our discussions with customers often revolve around evaluating product quality and consistency. In order to accurately evaluate your output, it’s important that you are screening a large enough sample set and are performing the evaluation in a consistent, repeatable manner. A simple example is the hardness test on a tablet. One must be able to take proper readings on the tablet many times throughout the process. The act of tablet evaluation should not interfere with the important production tasks while giving insight into product quality on the fly.
It is necessary to select a hardness tester that is capable of automatically handling an assortment of tablet sizes and shapes. Oblong, hexagon, diamond, and custom-designed shapes should be correctly oriented automatically and fed to sequential width, thickness, diameter, and hardness test positions.
How can solid oral dosage production be improved upon in the foreseeable future? Are there any practices that should be adopted in order to optimize the tablet press operation?
Specifically as it relates to physical evaluation of one’s product off the press, the automated Tablet Hardness Testers can be networked with a large variety of presses. Test data generated by a quality automated tablet tester can be electronically captured, stored and secured in a database or eLims system with CFR 21 Part 11 compliant software for further analysis. This data would be captured throughout the process and also communicated back to the press in order to make adjustments and maintain the quality of the product.
Can you talk about your technology and the features of your equipment?
To fulfill today’s requirements for features and technology that match the demand of QbD, it is very important to used technology like Auto Alignment to prevent erroneous hardness measurements. Auto Alignment is a patented feature on all SOTAX hardness testers that aligns the tablet in the correct position in the hardness station automatically, every time. The HT100 also includes features to ensure delivery of a single dosage to a scale for automated weight checking, a thickness gauge, and of course a linear load cell capable of consistent readings in a GMP environment.
Dr. Chuan-Yu (Charley) Wu
Senior Lecturer
School of Chemical Engineering, University of Birmingham
What challenges and trends are tablet manufacturing processes faced with today?
As tablets are the dominant dosage form that occupies two-thirds of the global pharmaceutical market, efficient tablet manufacturing processes is critical to produce safe, effective and affordable medicines for sustaining an effective health care system. For tablet manufacturing, it is technically challenging to ensure that tablets are produced with appropriate densities giving sufficient mechanical strength for subsequent coating, packaging and handling processes, and also satisfying the dispersion and dissolution requirements. Furthermore, intensive marketing competition has driven the development of novel tablet forms, including different shapes and adapting layered tablets. These novel forms have exacerbated the widely occurring problems of tablet failure during manufacturing, such as capping, where a conical segment detaches from the surface of a tablet, and lamination, where a tablet breaks into two or more laminated layers. Lamination has proved to be a particularly major problem in the production of layered tablets because of the inherent binding weakness at the bi-layer interface(s). Such failures during production can lead to enormous financial losses especially when costly drugs are involved. The current approach to addressing these problems is based mainly upon empirical trial-and-error, which is a time- consuming and expensive exercise.
However, pharmaceutical companies are subjecting to increasing pressure to control the growing cost to deliver and manufacture new products. Conventional trial-and-error pharmaceutical development approach and current batch-based manufacturing processes are struggling to meet the demand, as they are capital and labour intensive, high operating costs, low product yield, low utilization of the batch equipment (30%~40% on average), long lead-time due to stage and final product testing.
Continuous pharmaceutical manufacture is a promising alternative that can be used for conventional granulated products. This will increase the productivity with high yield, and reduce the operating and capital costs. Furthermore, it can reduce the variability of product properties with a thorough process understanding that is the key to develop a successful continuous pharmaceutical manufacture process. For continuous pharmaceutical manufacture, conventional trial-and-error approach is not feasible for drug development and manufacturing with APIs, because it requires a large amount of testing materials that is not generally available and is also very expensive. Therefore, innovative science-based methodology is urgently demanded. This includes, for example, predictive multi-scale models that can predict the performance of tablet manufacturing processes and the properties of the intermediate (e.g., granules) and final products (e.g. tablets) based upon the properties of individual particles.
Dale Natoli
President
Natoli Engineering Company, Inc.
What challenges and trends do you see for solid oral dosage equipment (or production in general) faced with today?
Trends: In regards to tablet compression tooling, one of the latest’s trends is multi-tipped tooling. What’s interesting is that the multi- tipped tool configuration has been used for hundreds of years, dating back as far as circa 1800. Multi-tipped tooling was first used with manual methods of tablet compression as a way to increase tablet production. Today the multi-tipped tool is gaining popularity for the exact same reasons: increasing tablet production. The multi-tipped tool configuration increases production in many cases over 200% without increasing real estate, operators or tableting machines. This provides a huge advantage by enhancing overall efficiency and reducing operating costs and maximizing tablet press utilization.
Not all products are eligible for multi-tipped tooling, where the common restriction is tablet size. In general, the tablet size in relationship to the punch type dictates the potential number of tips per punch, therefore the multi-tip tool is favored by manufactures of micro tablets or pellets which are typically coated for controlled release and filled into hard gelatin capsules.
Whether your tablet is industrial, confectionery, dietary supplement, or pharmaceutical, check with your tooling supplier to learn if your tablet is a candidate for the multi-tipped configuration and enjoy the benefits of increasing tablet production while reducing operating costs.
Challenges: There are many challenges regarding the compression of solid dosage forms. As long as there continues to be new scientific discoveries through research and development, there will always be new challenges. Each product or powder has its own unique characteristics, which react differently when introduced to the energy, friction and heat created during compaction. A phenomenon that continues to challenge the industry is sticking.
Sticking is the undesired adhesion of powders typically on the faces of the punches as well the adhesion of powder on the die wall and the outside circumference of the punch tip. Sticking generally results in secondary tablet inspection, press downtime, excessive labor, and unacceptable yields. Sticking is very costly and continues to be a challenge to the industry with a higher frequency when compressing dry blends.
I recently purchased reprints of a book published in 1906 titled Tablet Manufacture: Its History, Pharmacy and Practice, by Joseph Remington Wood. The book is very interesting as he addresses many of the same challenges the industry faces today. One of the challenges he describes is sticking, which he suggests wiping petroleum jelly onto the punch faces to remedy the problem!
As long as there is compression of powders and supplements there will be sticking. The real challenge lies in understanding what to do when sticking haunts your production and effects tablet quality, which could wind up costing millions of dollars. Many universities are proactive to understand and study the science of sticking. Pharmaceutical companies, tablet press manufactures and tooling suppliers have joined the bandwagon to help provide a practical solution for sticking.
How can solid oral dosage production be improved upon in the foreseeable future?
There are many ways oral dosage form production can and will be improved in the future. There are mechanical methods such as multiple tipped tools as discussed previously. There are unique tablet press designs eliminating the dies and the laborious task of cleaning, removing and replacing at the advantage of increasing the number of stations to enhance production. Mechanical improvement can only be as good or useful as the powder they handle. Powder flow, compressibility, particle size, and all other attributes that govern tablet production must be better understood to improve production and overall efficiency. Too many product development and research departments lack the proper equipment to facilitate a proper transfer of a product into production. Better understanding and, most importantly, relaying the idiosyncrasies of a product that can or will affect production will become more important as mechanical equipment production capacities continue to surpass the limitations of a formulation.
Proper and accurate communication is very important between all departments and persons involved with marketing, research, developing, quality, manufacturing, and packaging. Responsible parties should participate in group discussions and be given the opportunity to address foreseen pitfalls with a process, design or even production requirements to avoid production delays.
Are there any practices that should be adopted in order to optimize the tablet press operation?
Training, training, training! Optimizing the tablet press throughput requires a thorough understanding of the tablet press, the powder and the tooling. Understanding tooling and having knowledge of common tooling options is invaluable when trouble shooting tableting problems. Unfortunately, and very common even today, many tablet manufactures lack the personnel who possess a practical understanding of tablet compression tooling. Many companies overlook the need for proper tablet compression tool training, and yet it’s the tablet compression tooling that creates the tablet, the impression and perception of the tablet and its quality to the patient, care giver and consumer.
Can you talk about your technology and the features of your equipment?
In regards to tablet compression tooling support products, Natoli will soon be unveiling the newest technology for tool inspection. Our newest device is capable of measuring every dimension of the punch including cup radius, engraving and bisect in mere seconds. The feature benefit is the ability to measure surface finish of the punch cup to help determine the effect of surface finish for tablet quality and sticking. Our newest inspection device paired with Natoli TM-II tool management software is the most complete, effective and efficient system available.
Doug Kirsch
Technical Service Manager, Tablet Press Division
Natoli Engineering Company, Inc.
What challenges and trends are tablet compression operations (or processes) faced with today?
The challenges are much the same as they have been for more than 100 years. Higher tablet production, increased press efficiency and tablet uniformity have always been primary concerns. The basic design and operation of tablet presses has not changed in all these years. Granted, valuable “bells and whistles” have been added. Programmable Logic Controls, common on modern presses, reduce the chance of manufacturing tablets that are not within specification. Automatic weight control, tablet reject gates and a myriad of sensors and other automated controls have improved high-speed consistent tablet production. Yet, the venerable, old Stokes BB2, introduced in the 30’s, is capable of compressing high quality tablets, even by today’s standards, provided the formulation is designed properly. Too often tablet press and tooling manufacturers are tasked with resolving formulation related issues. In efforts to bring new products to market quickly, many times R&D is not given enough time or proper equipment to completely develop these prior to full-scale production. “Close enough” doesn’t work.
Whether due to product incompatibility or just for marketing reasons, layered tablets are once again a trend in tablet manufacturing. Layered tablets create a whole new set of challenges for the manufacturer.
How can the tablet manufacturing processes be improved upon in the foreseeable future?
One area that is often neglected is heat generation. Heat is the enemy of most formulations. We constantly hear “it ran well for the first hour or two and then it started picking or sticking”. Of course, after time the press warmed up and therefore, so did the tooling. Once the tooling becomes warm, or even hot in some cases, formulations are much more likely to pick or stick on the punch face. Natoli offers an optional chiller unit on one of its presses to combat this issue.
Other than the obvious causes of heat generation such as lack of lubrication or improper set up, I believe some press manufactures have reduced the clearances between the punch barrel and turret punch guide to the point where it actually exacerbates this problem. This was done in an effort to improve punch tip to die bore alignment, which is a great idea in theory. Unfortunately, thermal expansion seems to have been ignored. As the press warms up due to friction, motor and belt heat, the punch guides in the turret will decrease in diameter while the punch barrels will expand. This will reduce the needed clearance for lubrication, resulting in excessive heat generation or seizure of the tooling. More attention to this issue should be addressed with future tablet presses.
Are there any practices that should be adopted in order to optimize the tablet press operation?
Definitely! Tablet press operators and technicians require better training to increase production and tablet quality. Corporations will invest millions of dollars advertising their products, although they will not invest the small amount of funds required to properly train their operators and technicians. Yet, these are the very people responsible for meeting production schedules and ensuring tablet quality. Without these people there would not be much to advertise. Having been in this industry for more than 40 years, it amazes me how much the level of training and experience has declined in the industry over time. This is not to say operators and technicians do not take their jobs seriously. They want to do their jobs properly but are often not given the training or tools to do so. I do not know of a single press or tooling manufacturer that would dispute this statement, as many of their problems are due to this very reason. Well-trained, experienced press operators, press technicians and tooling technicians are essential to optimizing tablet press operation.
Domenick Salvemini
Sales Manager
Pharmatron, Inc.
What challenges and trends do you see for solid oral dosage equipment (or production in general) faced with today?
The pharmaceutical industry is in a constant shuffle of acquisitions, mergers and downsizing. With that being said, the need for equipment doesn’t necessarily decrease. While patents face expiration, there are other facilities who are looking to adding the product as a generic and increases their production and needs for equipment. Additionally, with the FDA having a watchful eye on GMP and focusing on the Nutraceutical and supplement industry, manufacturers are in the need for more sophisticated equipment and documentation.
How can solid oral dosage production be improved upon in the foreseeable future? Are there any practices that should be adopted in order to optimize the tablet press operation?
Automation is instrumental in providing consistent and timely quality assurance analysis. For example, implementation of automatic tablet testing equipment can eliminate the need of having a technician tediously handle and test individual samples for numerous parameters while also reducing personnel training and minimizing human errors. Automatic testers can consistently run samples and identify problematic circumstances before producing an extensive amount of costly, non-compliant product. Integrated central data collection applications also provide an excellent means to automatically document and store data while providing consistent information for audit trails.
Can you talk about your technology and the features of your equipment?
With more than 15’000 testers in the market, Dr. Schleuniger® Pharmatron has driven tablet hardness measuring technology for almost 40 years and has continuously set new industry standards by combining reliable precision mechanics with state-of-the-art electronics. Especially in the last 20 years, technological advances in electronics and software have continuously opened up new possibilities – allowing for a new level of precision measuring technology. Our latest models of tablet hardness testers and disintegration testers are specifically designed to increase user-friendly interfaces while increasing productivity and providing alternative data acquisition. We are continuing the advancement of technology with the introduction of several new products this year.