Pinpointing the Source of Tablet Spots and Specks

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.

Case study
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.

Possible causes 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:

• Over-lubricated upper punches

• Worn, faulty, or missing dust cups

• Sloppy, worn upper-punch bores

• 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

• Poor punch quality and/or maintenance.

Potential solutions
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.

Case of the blue spots resolved
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.

Keep an open mind
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.

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