Matt Bundenthal is direct sales and communications manager at Fette Compacting America, www.fetteamerica.com .

Matt Bundenthal

Tablet manufacturing is evolving, and the use of highly potent active pharmaceutical ingredients (HPAPIs) is increasingly prevalent. The inhalation of hazardous, airborne particulates can represent a real risk for those operating the equipment used to compress final tablets. It is due largely to these facts that the concept of contained tableting equipment is gaining prominence in pharmaceutical manufacturing facilities. 

	Any discussion of containment involving pharmaceutical tablet compression is likely to include a number of common acronyms. The following are some of those most commonly encountered:

		Occupational exposure banding (OEB) is a process whereby APIs are assessed and categorized for toxicological concentration. 

		Occupational exposure limit (OEL) is an upper limit on the acceptable concentration of an airborne particulate API, in terms of the risk associated with an individual’s exposure to the API, usually expressed as a value of micrograms per cubic meter (µg/m³).

		Permitted daily exposure (PDE) is the amount of a specific active substance for which the occurrence of an adverse effect is unlikely in an individual exposed to this dose, or to lower values, for a lifetime (1).

		Personal protective equipment (PPE) is clothing, respirators, etc. used to create a protective barrier between operators and potentially toxic substances.

depicts the various topics of consideration that come into play when operator safety is considered. A product should be initially assessed for the amount of dust it is capable of creating, as well as the amount of highly active substance it contains relative to its overall dosage (i.e., dilution). The manufacturer will also need to decide what protective measures to take with regards to the operator-which may well include the use of PPE-and how it will quantify the risk levels associated with a particular product (i.e., measurement protocols). Finally, after determining that a particular product does, in fact, constitute an exposure risk for the operator, consideration may be given to the use of specialized technology that includes features specifically designed to contain dust or allow for precleaning prior to breaching containment, for example, thereby mitigating the risk factors.  

	Different end users will employ different strategies for protecting their equipment operators, but what remains constant across manufacturers is a legal obligation for taking such measures. Containment solutions must ensure that established limit values for highly active ingredients can be reliably maintained during the manufacturing process. The International Society for Pharmaceutical Engineering (ISPE) 

 acts as a guidepost for technical solutions pertaining to hazardous substance handling in pharmaceutical facilities and can provide further information (2).  

depicts the relationship between OEB bands and OEL or PDE limits, illustrating how equipment users can identify the level of containment to be considered for various applications. It is important to mention that while the OEB and OEL categories do quantify limit levels, their interpretation and the way that various end users will seek to achieve operator safety can be highly variable.

	Different containment requirements necessitate a wide array of equipment needs, and many tablet press vendors offer options that are suitably configurable. It is imperative to note that containment projects are inherently complicated, both from an equipment and facilities perspective. Consider the following steps. 


	The first step is to determine if a particular active ingredient is potentially hazardous enough to those working with it, such that it warrants the use of contained equipment in the first place. There are differing philosophies on how best to approach such situations, which can include the avoidance of the ingredient all together (essentially a fool-proof approach), the use of PPE alone (the least effective approach), or something in between. 


	Once a determination has been made that an ingredient does have associated risks, it is time to define them. The OEB data shown in 

are the rule of thumb for pharmaceutical manufacturers seeking to quantify a risk level. These categories, when considered in addition to the drug load for a particular product (i.e., the ratio of active ingredient to the overall dosage or dilution), will lead to greater clarity in terms of what level of equipment containment is actually necessary. 

	Although the scope of this article does not allow for a detailed exploration of personal protective equipment (PPE), it should be noted that those having the most experience with compressing highly active substances generally elect to use some form of PPE, regardless of the efficacy of the contained system being utilized. PPE can be important given the fact that with virtually all contained systems, final cleaning will still include manual steps.


	Identify equipment manufacturers that can meet your needs and who, ideally, have a proven track record with such applications. Asking for surrogate test results is a good way of vetting for this purpose. Qualified vendors will not only perform such testing, but also offer systematic methodology for scientifically matching a specific containment target (when one has been clearly stated) to a well-defined equipment system. This testing can bolster internal risk-assessment processes the end user conducts under ISPE’s Standardized Measurement of Equipment Particulate Airborne Concentration guidelines (3), as the methodology itself will result in a standardized, objective, and reproducible determination of a specific system’s capabilities.

Select containment-specific features and attributes.


	Identify the level of containment the press will need to maintain and select the options necessary for reaching that goal. For example, an ingredient with an OEL level of 50 µg/m³ (OEB 3) will commonly require less containment than one with a level of 8 µg/m³ (OEB 4).

	If a particular set of containment-related requirements necessitate dry-clean, low-dust production only, then a press fitted with glove- and rapid transfer ports, as well as need-specific process equipment, may prove to be the ideal fit. Glove ports typically utilize fail-safe technology that prohibits the operator from gaining access while a press is running. When the machine is in a static state, the ports provide access to the interior of the press for simple operations such as cleaning a punch tip or changing a fill cam, without breaching containment. A rapid-transfer port allows for either introducing a small component into the press or removing it, similarly without a breach. Utilizing split-valve technology for charging the press, in addition to high efficiency particulate air (HEPA) filtration and dust-tight discharge chutes, applicable models that are correctly configured can potentially provide containment levels of approximately 5 µg/m³ (i.e., the middle of the OEB 4 band).  

	Hazardous active ingredients necessitating wet cleaning, where the press will run itself through various wash and rinse cycles (i.e., wash-in-place systems), are often classified at the higher levels of the OEB 4 band and into OEB 5 or above. Such press systems are far more complex and are designed to introduce various forms of water and detergent into the machines. This set-up allows for the binding of airborne particulates with water molecules, which are then drained away before access doors are opened. Integrated, internal spray wands may be available, with which the operator can essentially pre-clean the compression zone prior to letting the automated wash system perform its function. For OEB 5 applications, process equipment such as de-dusters, metalcheck units, and quality control testers may be installed in separate but connected isolators, ensuring that the entire tableting system is fully contained and safe. When tackling these products that warrant higher levels of containment, sophisticated air management systems are available that provide automated safeguards against risk factors, such as power loss, and maintain predetermined set points (i.e., vacuum) across variable run conditions. The caveat to the latter approach is that project costs are generally much higher, as related equipment and facility considerations are proportionately more complex.


	Due to this inherent complexity of containment projects, whether they necessitate dry- or wet-cleaning, they always present challenges extending beyond those of a non-contained endeavor. It is therefore strongly recommended that end users identify their equipment vendors as far in advance as possible. Making a selection early will allow for the commencement of project-critical dialogue between the end user and their chosen supplier. It should also be worth noting that contained presses often have lead-times of up to 50% longer than their non-contained counterparts. 

	The sole purpose of investing in contained compression equipment is to ensure the safety of one’s operators. Nothing else could, or should, be of more paramount importance. Take the time to properly identify potential risk factors, methodically match those factors to suitable equipment, and create a safer, more efficient working environment. 

	The author would like to thank Dr. Martin Schöler (author of

, Fette Compacting GmbH, 2019) for his constructive insight and feedback during the creation of this article. 

Guideline On Setting Health-Based Exposure Limits For Use In Risk Identification In The Manufacture Of Different Medicinal Products In Shared Facilities.

European Medicines Agency, Committee For Medicinal Products For Human Use (CHMP), Guideline EMA / CHMP / CVMP / SWP / 169430/2012, 2014

Community of Practice (CoP) Containment D/A/CH Affiliate: Containment Manual 

ISPE Good Practice Guide: Assessing the Particulate Containment Performance of Pharmaceutical Equipment 

	Matt Bundenthal is director of sales and marketing at Fette Compacting America.


	Vol. 44, No. 4
	April 2020
	Pages: 34–37

	When referring to this article, please cite it as M. Bundenthal, “Understanding Containment for Tableting," 

Articles

Risk levels should be considered when designing containment for pharmaceutical tableting equipment to enhance operator safety.

Understanding Containment for Tableting

Oral solid dosage drug manufacturers are regularly faced with making substantial equipment investments, and that certainly applies to rotary tablet presses. Although modern presses do boast the potential for lengthy, useful lives, the efforts made to exploit that should always be commensurate with the scope of the initial capital outlay. Increasing economic pressures have resulted in efforts to pay closer attention to preventive maintenance, although there comes a time when equipment refurbishment may prove absolutely necessary.

	Original equipment manufacturers (OEMs) are often, and not surprisingly, an invaluable source of recommendations on how to maintain presses properly. Many also offer their own refurbishment services, thus one can turn to them for advice on what to look out for, and the best methods for undertaking such endeavors. It is the goal of this article to suggest some guideposts for approaching the idea of refurbishment, when such has been deemed necessary. 

	The decision on when to refurbish a machine will depend largely on the press owner, their own standard operating procedures for preventive maintenance, and whether or not their approach to this maintenance is proactive or reactive. There are, however, some rather obvious indicators that refurbishment work may be a good idea. Some common warning signs on a tablet press may include:

		Erratic compression forces: potentially attributable to various issues, including those relating to load cells and poor calibration

		Poor or inconsistent weight control: variable causes, such as bad punch seals, worn dosing station gearboxes, worn or damaged cams

		“Chatter” in the compression stations: a possible sign of bad shims, bearings, etc.

		Odd noises from the main drive compartment

		Traces of product in undesired locations: worn parts, especially seals, can allow product to migrate into places that it ordinarily should not

		Excessive vibration: a sure sign of mechanical trouble that can have a snowball effect on other parts

		Excessive wear on parts that should not ordinarily wear out (i.e., compression rolls, feeder tables, which normally rely on good runout of an in-specification turret)

		Another major catalyst for considering the idea of refurbishment is the specter of looming obsolescence on certain components. One should always make it a practice to periodically ask the OEM for any indications that certain assemblies may soon become obsolete and to plan for such eventualities.

	It is crucial for the press owner to identify the degree to which they wish to refurbish their press, early on in the process. This planning prevents the problem similar to that found when one brings a car to a mechanic for one issue but is ultimately informed that everything needs to be replaced. Refurbishment costs can spiral out of control should this important step be overlooked. Some press users simply wish to ensure their machine is brought back to a state of mechanical soundness; others wish for the same, but also strive for cosmetic improvements and computer upgrades.

	The ideal way to approach a repair or refurbishment endeavor is to have an OEM representative physically pre-inspect a press at the user’s site. Much guesswork is thus removed, and it will foster a clearer understanding of scope and projected costs. This understanding often facilitates the prioritization process for the press owner, allowing them to budget for repairs and improvements deemed absolutely necessary. It is strongly recommended that the user pursues such an inspection, and requests a detailed quotation, prior to any work commencing (especially for projects necessitating the press be shipped elsewhere for work to be performed). 

	There are some other important items to think about when considering refurbishment, especially if the work is to be performed by another party:

		Will there be warranty coverage following the work? If so, what is covered and for how long?

		Does the current condition of the machine actually justify significant refurbishment expenses? Does it have a good, undamaged foundation on which to base all other work? 

		If a machine is particularly old (i.e., 25+ years) does it make sense to invest significant capital into mechanical and computer upgrades, when certain electrical components that are too complicated to remove and replace are likely to always lag behind? Full computer system upgrades can be costly.

		If the refurbishment work is to be performed by a third party, including an OEM, be sure that a comprehensive list of parts replaced will be included after the work is complete.

		It is strongly recommended that work should progress in a fashion similar to that embraced by the OEMs (if the OEM is not performing the work themselves). Many older tablet presses have seen years of steady use, and will therefore be hiding dirt, grease, and other undesirable substances in hard-to-reach places. Modern presses are highly precise machines. If one wishes to restore a press to a “like-new” condition, so that it ultimately performs as originally intended, it is strongly recommended that a rebuild should begin by stripping the machine down to its frame, followed by pressure washing. It is from that point that one has an optimal base on which to build things out.

	While the order in which things should be checked may vary, the following items should always be carefully considered when performing refurbishment work on a tablet press. In all cases, repair or replacement of faulty and worn components should follow, as applicable.

The turret assembly represents the core of any tablet press, and it is the most tolerance-critical component. It should be inspected for excessive wear or damage. Punch bores, die cavities, and the die table surface should be checked. Runout, the uneven wear found at the outer edge of the turret, should be minimal (if it exists at all). 

All cams and cam tracks should be carefully inspected for excessive wear and/or damage. Lower punches that drop lower than they should can contribute to erratic weights and low yields. Worn cams can allow for other unintended punch movements, leading to premature wear of other parts that come into contact with the punches.

Compression roll surfaces and bearings should be inspected for surface wear and/or excessive “play.” Rolls exhibiting any form of pitting should always be replaced; if metal fragments adhere to punch heads they will be transferred to the next roll, creating other pits, and so on.

All adjustment gearboxes (i.e., for compression and dosing stations) should be inspected such that factory specifications can be maintained. These components play a major role in maintaining the precise volumetric control that modern presses are capable of.

Load cells should be tested and verified for normal operation; “weight” control on a tablet press is typically derived from force measurement at the compression station load cells, thereby necessitating good signal strength and clarity.

The main drive should be inspected and cleaned. The main drive gearbox should be inspected for excessive wear and/or “play.”

Discharge chutes and ejection assemblies (where applicable) should be inspected and tested for proper function; very minor adjustments to these components can make the difference between good yields and a clean room, or tablets flying all about.

Shrouding should be inspected and proper fitment confirmed; a metal shroud that makes even minimal contact with a rotating turret, for just one revolution, can instantly create lasting damage.

Electrical and safety interlocks should be carefully checked for proper function; tablet presses contain some very heavy components that move at high speed, and such inertia should be respected by ensuring all safety features are performing as intended.

	When electing to have refurbishment work performed by an OEM, minor cosmetic damage is typically covered by an initial proposal; more substantial cosmetic needs, uncovered during in-depth dismantling and assessment, should be agreed to only after consultation with, and approval by, the press owner. As stated previously, one should practice due diligence before embarking on a refurbishment project and decide early on as to what is critical versus what is unnecessary. This is especially important when the work is to be performed by a party other than the end user themselves, or an OEM.

	Given the level of sophistication found in most modern tablet presses, including many of those built as many as 20 years ago, refurbishment work should include the calibration of all applicable equipment and devices (i.e., load cells, compression roll gearboxes, dosing stations, etc.). Calibrating the various sub-assemblies should be considered of paramount importance, and all efforts should be made to calibrate to the OEM’s original factory specifications. Proof of the procedures having been performed, normally in the form of a calibration sticker, should ultimately be affixed to the equipment.

	Tablet presses are generally capable of impressive performance, but the most sophisticated examples are made up of many hundreds of different parts that must work in concert with one another. It often takes only one or two off-song components to ruin the show. The good news is that, barring extreme damage, most presses can be brought back to a level of original factory performance, provided the owner embarks upon a sensible refurbishment program.

	Take the time to consult with your OEM, as they are bound to have information that is unavailable elsewhere. It is likely they may offer their own refurbishment services, and chances are there are few, if any, things to be found that will surprise or confound their technicians. Detailed repairs and detailed refurbishment deserve detailed know-how.  The improvements most commonly reported by press owners who have undertaken a careful refurbishment program are those leading to greatly improved yields, which is of primary importance for tablet manufacturing. 


	Vol. 43, No. 3
	March 2019
	Pages: 32–35

	When referring to this article, please cite it as M. Bundenthal "Tablet Press Refurbishment: Why and How?" 

	Matt Bundenthal is director, sales and marketing at Fette Compacting America, 

Identify the warning signs and follow best practices for refurbishment to improve tablet press yields.

Tablet Press Refurbishment: Why and How?

	Finding an ideal balance between high speed and precision on a modern tablet press-to optimize the ratio between bulk product introduced into the feed hopper and the acceptable tablets that exit the discharge chute (i.e., yield)-is likely to rank number one on any end user’s priority list. Paradoxically, the attainment of idealized yields often remains the most elusive goal in the compression suite. This article  sheds light on factors that affect yield and how to improve them.

	Reaching an optimal yield state is predicated on getting the most bulk powder into the die cavities between punches and, ultimately, into finished tablets. It is not just about making the press look clean, with minimal dust and mess. One can easily reduce the mess made on a press by simply using maximum vacuum, running the press slowly, or indiscriminately scraping excess powder away from the die cavities. These examples, however, will not improve final yields, as the goal is to put the maximum (but desired) amount of powder 

 the cavities, rather than directing it elsewhere.

	Most modern pharmaceutical manufacturers using state-of-the-art tablet presses will look to achieve final yields as high as 99% for single-layer tablets. Multi-layer yields are more challenging, given the number of different variables involved, with realistic figures often dipping closer to 85%. Multi-layer yields can be as high as 92%, however,  on a press with excellent first-layer sampling features; sampling frequency, and the time it takes to cycle through a sample, can be precisely adjusted on select presses, resulting in significantly improved yields.

	The best first step in attaining optimal, repeatable results is systematic training. Operators and set-up technicians should, ideally, participate in and successfully complete a formal, comprehensive training program, which are offered by equipment vendors.  The best programs will teach about all of the contributing factors discussed in the following section, all of which have a strong influence on product yields.

 Perhaps somewhat obvious, but often overlooked, poor hopper seals can cause a surprising amount of product loss, especially over the course of an entire batch. Product can escape either from the top seal, where the hopper is connected to an overhead feed system, and/or from the bottom, where it connects to the feeder assembly. The following are some recommendations for hopper seals:

		Consider the use of tri-clamp fittings, which provide more robust connections between components.

		If silicon (or similar) caps are used, ensure they are checked regularly for wear; replace as necessary as part of a systematic preventive maintenance program.

		Periodically observe both upper and lower connections over the course of a run.

 The correct positioning of an induced feeder can prove a fickle undertaking, which is probably why it is so often a major cause of product loss. Some degree of space must exist between the base of the feeder and the die table surface passing beneath it, but the optimal setting of this gap will vary across products. Leveling the feeder is also a significant concern, as an uneven feeder will invariably lead to premature wearing of other components. The following are recommendations for feeder positioning:

		Make certain that operators have been trained by the tablet press manufacturer. The procedures for properly setting a feeder often include nuances not obvious to the end user. Make it a point during the initial commissioning of a new press to request that this topic is one of those prioritized by the vendor’s representative technician.

		Invest in supplementary training materials and software that specifically cover the setting and adjustment of a feeder assembly.

		Request written feeder set-up procedures from the vendor.

 Just as important as a feeder’s positioning is the installation, condition, and efficacy of the seals used beneath the feeder, in its base, to ensure that product is effectively contained and that only the desired amount reaches the die cavities. Worn seals lead to measurable product loss. There are many types of seals in use, but the best mitigate the effects of heat while also offering easy installation and removal. The following are recommendations for feeder seals:

		Ensure that operators are systematically examining feeder seals each time the feeder is removed from the tablet press, searching for signs of wear or excessive abrasion.

		Make the replacement of worn seals part of a comprehensive, regular preventive maintenance schedule.

		Consider the use of feeders that offer sealing options for different fill channel widths. Some vendors offer styles that can be tailored to the specific size of different tablets: wider widths for larger tablets, narrower widths for smaller tablets. The closer that one can match the width of the fill channel to the actual size of the tablet, the smaller the product losses incurred.

 Fill cams play an integral role in making tablets. The filling process is similar from one press to the next, in that the fill cam allows the lower punches to be pulled down farther than they really need to go, thereby ensuring enough powder is in the die cavity to start (i.e., over-filling). A dosing cam will then “dose out” (i.e., push) a quantity from the die, such that the amount of product left in the cavity just prior to the upper punch making its entry is exactly how much is necessary for reaching target tablet weights. It is important that set-up technicians do not default to choosing fill cams with a filling range larger than necessary for a particular tablet weight. The following are recommendations for fill cam sizing:

		Stick to the “80%” rule; using 80% of a fill cam’s nominal range for achieving target weights is the best prevention for cam-related product loss.

		Ensure that operators are systematically examining fill cams each time tooling is removed from the tablet press, searching for signs of wear or excessive abrasion.

		Make the replacement of worn fill cams part of a comprehensive, regular preventive maintenance schedule; use of cams that have worn outside of their original, intended range will result not only in product loss, but also erratic tablet weights.

		Use original equipment manufacturer (OEM) fill cams, whenever possible. Fill cams have a direct and incontrovertible effect on final tablet quality, as they are tolerance-specific; the use of non-OEM supply for such parts often proves a risky proposition.

		Consider the use of a fill cam wear tool; some press manufacturers make their own.             

 The use of new, or at least well-maintained, tooling should be a cornerstone guideline. Sloppy tolerances on inferior or worn tools will contribute to product loss, sometimes in a fashion that is hard to detect. The following are recommendations for tooling tolerances:

		Invest in quality tooling in the first place.

		Use “matched” tools, where particular punches and dies are paired.

		Implement and adhere to a regimented preventive maintenance program, as recommended by any of the leading tooling manufacturers.

		Use quality measuring equipment for in-house maintenance.

		Ensure dies are seated properly; their tops should not rise above or sit below the surface of the die table.

		If using tapered dies, endeavor to keep the tapering to a minimum.

Condition and positioning of product scrapers.

 Modifying the position of scrapers can certainly affect product yields. The scrapers that follow the feeder, just prior to upper punch penetration of the die, are there to ensure product stays in the cavity where it belongs. Other scrapers are intended to direct any excess powder into a recirculation channel (if the press in question is so equipped), such that it can ultimately be returned to the entry side of the induced feeder. The following are recommendations for condition and positioning of product scrapers:

		Review the operating and cleaning manuals as provided by the tablet press vendor and adhere to the standard operating procedures (SOPs) for set-up.

		Ensure that operators are systematically examining all scrapers each time the tablet press is serviced and/or when a product change occurs.

		Make the replacement of worn or suspect scrapers part of a comprehensive, regular preventive maintenance schedule.

 The depth to which the upper punch penetrates a die presents opportunities for effectively containing product (thereby improving yields), but it’s another case of finding the “sweet spot.” Generally, if penetration depth is too shallow, it is likely powder will be blown out of the dies as the punch penetrates. If the penetration is too deep, the risk of entrapping too much air increases, resulting in another undesirable compression phenomenon known as “capping” (in which the finished tablets split into two pieces). The following are recommendations for upper punch penetration depth:

		Methods for finding optimal penetration depths should be discussed during a machine’s initial commissioning, while the vendor’s representative technician is on-site; make it a point to ensure this specific topic is covered during the installation and training period.

		For existing presses, contact the vendor and request guidance and reference materials for setting the penetration depth.

		If working with placebo, experiment with various penetration depths, ideally with the use of a high-speed camera to observe exactly what happens as the upper punch enters the die.

		Exercise caution when adjusting the penetration depth on presses that do not synchronously adjust the lower stations while the uppers are in motion; there is a risk of the upper and lower punch tips colliding if the upper punch penetration is too deep.

 Most modern tablet presses offer some form of recirculation features, which are specifically intended to guide any excess powder around the inner circumference of the turret and ultimately return it to the induced feeder. This end goal is accomplished through the use of strategically placed scrapers, a channel and, in many cases, a “plough.” It is common, however, for the adjustment of these parts to be off by just enough to negatively affect final yields. The following are recommendations for using recirculation features::

		The methods for properly positioning recirculation components should be discussed during a machine’s initial commissioning, while the vendor’s representative technician is on-site; make it a point to ensure this specific topic is covered at that time.

		For existing presses, contact the vendor and request guidance and reference materials for setting recirculation components.

		Reference the operating manuals and SOPs as provided by the tablet press vendor, and adhere to procedures as outlined therein.

 Virtually all tablet presses make use of some system for vacuuming excess powder from the die table surface. Excessive vacuum, however, can actually pull good product away from the die cavities, or elsewhere, resulting in unwanted losses. The following are recommendations for vacuum settings:

		Follow the vendor-supplied SOPs for guidelines on optimal vacuum settings.

		Make a measured assessment of the vacuum in the compression suite and compare it to the press vendor’s recommended specifications.

		Consider presses that have automatic “damping” valves in their extraction system, which allow for the modulation of how much vacuum is applied at the turret-mounted extraction ports.

 Computer-controlled presses generally allow the user to configure a parameter for rejecting a certain number of tablets every time the machine is started, in certain modes. These features are offered due to the risk of producing out-of-specification, “transitional” tablets as the machine ramps up to operating speed and to help mitigate the risk of those tablets finding their way into the good tablet channel. The following are recommendations for start-up reject settings:

		Pay close attention to the vendor-supplied operating manuals, as most will provide detailed explanations for all possible parameter settings.

		Consult onboard help functions, if available.

		For new press installations, encourage operators to request specific guidance for parameter set-up from the vendor’s representative technician.

	Many tablet manufacturers are compressing products that contain increasingly expensive active ingredients or, at a minimum, are implementing overall efficiency programs. It is thus of paramount importance to embrace good manufacturing practices, with an eye towards maximizing product yields.

	Newer presses generally have features that will help prevent product loss, but this fact should never absolve the end user from maintaining a press to the highest standards and regularly implementing good usage habits to fully understand what impact those features have on final tablet quality and overall efficiency.

	Take advantage of the resources available from a tablet press vendor and regularly request new or revised SOPs for operation, cleaning, and maintenance. Participate in training seminars whenever possible. Your yields may depend on it.

:
	When referring to this article, please cite it as M. Bundenthal, " Optimizing Yields on Modern Tablet Presses," 


	Matt Bundenthal is direct sales and communications manager at Fette Compacting America, www.fetteamerica.com.

Learn how to prevent common causes of product loss.

Optimizing Yields on Modern Tablet Presses

	Finding an ideal balance between high speed and precision on a modern tablet press-to optimize the ratio between bulk product introduced into the feed hopper and the acceptable tablets that exit the discharge chute (i.e., yield)-is likely to rank number one on any end user’s priority list. Paradoxically, the attainment of idealized yields often remains the most elusive goal in the compression suite. This article sheds light on factors that affect yield and how to improve them.

	Preventive maintenance (PM) is something that pharmaceutical manufacturers should employ on a regular basis, though it remains somewhat alarming to see how many wait until they experience an “uh-oh” moment before acting. Tablet-press manufacturers can offer varying guideposts for the timing of such PM intervals, but there are some easy signals to remain cognizant of that should prompt proactive behavior. A few of these include odd noises, erratic tablet weights, and premature wear on contact parts such as cams and compression rolls. Today’s presses can produce tablets at an astounding rate, with extraordinary accuracy, but only when they are looked after in meticulous fashion.

	The most effective PM is that which is performed on an almost daily basis, even if only implemented informally. Adherence to such methodology will not only ensure that the tablet press itself remains in like-new condition, but that it also continues to compress tablets that strictly conform to the target physical parameters as mandated by the user. The importance of paying such consistent attention to the condition of one’s press increases to an even greater degree in some specific cases, such as when employing higher compression forces (e.g., those regularly in excess of 50 kN).

	Any regimented inspection program on a modern tablet press will examine components including:

	Some tablet-press suppliers offer their own programs that will, in turn, augment those put in place by the user. The suppliers retain the advantage of understanding exactly 

 their machines were designed in a particular fashion, and their employees often retain encyclopedic knowledge of subtle features and procedures. A supplier-driven program typically includes a visit from a service technician who performs a thorough assessment of each installed press. Goals of such a program will typically include:

		identification and replacement of worn or non-working components

		simplification of standard operating procedures and implementation of checklists

		equipment-based suggestions for improved yields and production rates

		introduction of new enhancements, features, and upgrades

		implementation of various training programs

		user team formation and goal setting for improved efficiencies and decreased changeover times

		heightened awareness of safety inspections and use of installed safety features

		a direct link to related initiatives, such as overall equipment effectiveness (OEE).

	Arguably the most valuable aspect of this type of program is the fact that the press manufacturer will provide a detailed summary analysis of their findings. Such analyses succinctly capture all pertinent facts but also provide a guideline that the user can reference for their own preventive procedures. Tablet presses represent some of the most significant equipment-specific investments a solid-dosage manufacturer will make, and the care afforded them should be commensurate.


	Matt Bundenthal is direct sales and communications manager at Fette Compacting America, 

Tablet presses require regular inspection and maintenance to prevent premature wear and tableting problems.

Best Practice: Preventive Maintenance Keeps Tablet Presses Running Smoothly

	Manufacturers of tablets have long battled a host of occasional but common issues that can be alternately irritating and serious. Tablet defects can be purely cosmetic or they can be related to problems such as incorrect dosages, resulting in a potentially dangerous situation for consumers (too much or too little active ingredient in the finished tablet), loss of revenue due to excessive rejects and waste, and/or issues with downstream equipment. A few of the more common issues well-known for causing headaches for experienced compression personnel include:

		Capping: a splitting of the tablet and its “cap,” occurring at the top of the perimeter band

		Picking: product sticking to the punch tip within an embossed area

		Laminating: a lateral fracture within the tablet

		Sticking: product adhering to the face of the punch tip

		Spots or specks: undesirable visual flaws that can be superficial and/or embedded within a tablet.

	This article addresses the problem of spots or specks. Commonly referred to by the over-generalizing term “black spots,” these unsightly blemishes or foreign substances should more appropriately be categorized as any spots or specks that are not supposed to appear in the first place, but that in most cases are easily (and visually) detectable. Spots are generally those imperfections that reside on the surface of the tablet only, while specks can be present throughout a tablet. Specks are sometimes visible on the surface, sometimes hidden inside, or both. It is important to note that undesirable spots or specks can be gray, black, or almost any other color, even white.

	Manufacturers battling a spot or speck issue can occasionally find themselves with a simple, easy-to-find solution. Conversely, they can also bang their heads against the proverbial wall in their effort to unmask a source. Unless it is by design that spots or specks are on or in a tablet, their presence clearly calls for swift remedial action. The aim of this article is not to try and provide an exhaustive list of all possible sources for the intruders, but rather to point out that said sources are not always obvious and, in some instances, will warrant an investigative effort Sherlock Holmes would envy. Regardless, a reputable manufacturer will attempt to rapidly pinpoint the source of the issue and eradicate it.


	A reputable pharmaceutical manufacturer discovered spots in one of their products-a tablet-prompting an immediate and exhaustive investigation. At the outset, optimism reigned for quickly determining the root cause of the spots because they were, in fact, blue. Despite a methodical, intensive process of elimination, however, the manufacturer could not locate any material within the manufacturing line or raw material that matched the color of the spots appearing in the finished tablets. The ultimate resolution of this atypical issue will be discussed after first examining some of the more common sources of spots and specks.


	Although it often proves true that an oil-based issue on the tablet press is the culprit, the following are other potential sources:

		Reactions between incompatible material combinations (e.g., certain active ingredients will turn darker when subjected to high heat or when mixed with particular tooling lubricants)

		A “slinging” effect at excessively high turret speeds, where an accumulated product-lubricant mix is thrown from the punch barrel

		Poor or inadequate cleaning procedures, especially between product changes

		Upstream origins (e.g., contaminated raw materials, blending issues, dislodging of grease and lubricants on mixers or granulators)

		Improper product-specific gaps between feeder base plates and the turret surface; too-tight gaps can cause some particle sizes to “roll” and ultimately change color


	The best possible solution for an issue with spots on tablets is to consistently employ methods for avoiding them in the first place. This may appear obvious, but in reality, tablet press operators often deviate from GMP methodology, especially in terms of following recommended guidelines for cleaning and set-up as provided by original equipment manufacturers (OEMs). If not already in possession of such procedures, every company should poll their suppliers for them and implement their contents into a cohesive and all-encompassing set of standard operating procedures (SOPs).

	Having stated the above as a best line of first defense, strict adherence to good SOPs cannot supersede all potential issues. Some suggested guidelines for eliminating spots when they do appear, or for helping to prevent their occurrence at all, include:

		Optimizing lubrication settings, including dose rate, interval, and duration, especially for upper punches; documents and suggestions from the OEM should help here

		Regular use, and replacement of, quality dust cups; they are easy to install and are disposable

		Regular use, and replacement of, upper punch seals (on presses that offer them as an option)

		Use of punch bellows, especially for particularly dirty products or those necessitating the use of maximum upper lubrication; bellows can actually prevent the mixing of lubricant and dust in the first place, greatly reducing the likelihood of eventual spots

		Strict adherence to SOPs for cleaning and set-up

		The use of equipment manufacturer-recommended vacuum settings

		Judicious inspection and replacement of “contact” parts, such as feeder base plate seals and “tail-over-die” scrapers

		Regular inspection of seals and/or gaskets located within mechanical feeders

		A systematic inspection of all product-contact areas within the entire manufacturing line where an oil or other lubricant may be used.

	If, indeed, raw material issues are ruled out and a press manufacturer is asked to recommend a first place to look, most will generally suggest the bottom of the barrels on the upper punches, where the punches protrude from the upper punch ring. A quick visual inspection can detect any unusual build-up of material and excessive lubricant that may be contributing to a problem. If present, it should then prove easier to put a stop to the offense.

	Depending on the severity of the issue and the company experiencing it, some will seek independent analysis from a third-party laboratory in an effort to determine the source and composition of the spots. It is, however, important to note that the success of such an investigation can vary considerably. Certainly there are times where the lab can shine the brightest light on a shadowy issue, while just as frequently the offending contaminant is identified and confirmed locally, at the floor level.


	Having turned over virtually every imaginable rock in their quest to locate the source of the blue spots referenced earlier in this article, the manufacturer had come up with no cause, only effect--no means, only ends. Not until the completion of a blending campaign that spanned multiple days did they, quite by accident, finally uncover causality. While cleaning the flange on a V-blender, a maintenance technician noticed blue material resembling that which plagued the final tablets. It was ultimately determined that airborne particles of the active material were sticking to a white anti-seizing compound used on the flange bolts, agglomerating there and ultimately falling through the flange and into the blend destined for compression. There it remained undetected, even throughout the compression cycle (it was still white at the time) until, after approximately 48 hours, a chemical reaction would occur, turning the spots blue.


	As is the case with so many undesirable equipment issues, regular and judicious training (and retraining) can have a positive effect on the prevention and elimination of spots. One item to mention of paramount importance is that tablet manufacturers must keep an open, inquiring mind when seeking to identify those factors contributing to such an issue. Although problems may often have their genesis with something local to the tablet press, this is most definitely not always the case, as shown with the case study example. If raw material contamination can be ruled out early on, then the investigator must bear in mind that the source of spots can originate at any location where product makes contact with another surface or substance, be it prior to, during, or following compression, even if said contact does not immediately result in the undesirable defect. Be prepared to grab an oar and row against the current, as the solution to your problem might just be upstream.

Solving the problem of tablet spots or specks involves prevention and thorough investigation.