Reprinted From September 2004 www.tabletscapsules.com tablet press operation Preventing and fixing weight and Michael D. Tousey DI Pharma Tech hardness defects: Strategies for production personnel Tablet specifications are tight, and the list of possible defects is long: Variable weight, sticking, picking, black spots, streaks, capping, lamination, variable hardness, among others. This article focuses on variations in tablet weight and tablet hard- ness. It pinpoints the possible causes of these defects and offers E very product behaves differently on a tablet press, even if it’s the same product run on a different day. The variation often stems from changes in the properties of the raw materials—active ingredients and excipients— from batch to batch. Naturally, the goal is to minimize these changes. Tablet press operators, however, don’t advice on preventing and fixing the source of the problems. It have any control over formulation and granulation. They also discusses the problems of formulations with too many have to work with what they’re given, and their employ- ers expect them to make good tablets day in, day out. fines. Tablet weight: Sources of variation Tablet press adjustments If you’re a tablet press operator, the exchange below As the tablet press operator, your job is to make good may have a familiar ring to it. tablets, no matter how poorly the product works on the Tablet press operator: It says right here that if the operator tablet press. Here are some things you can adjust on the cannot maintain target weights within acceptable quality tablet press to overcome weight variations. Refer to limits that I must report to you, my supervisor. So what Figure 1. should I do? Supervisor: You’re the operator. How’d you do it last Figure 1 time? It worked fine on the last batch, right? Operator: I didn’t do anything differently. It must be the An illustration of the compression cycle product. So what do you want me do? 9 10 Courtesy of the American Pharmaceutical Association Supervisor: Let’s pull out the checklist and review the options. 6 7 8 So the two of them scan the checklist on weight con- trol, which tells them that tablet weights are mainly affected by 1 2 1. Product variation 2. Machine condition 3 3. Tooling condition 4 5 4. Flow of powder on the machine Let’s look at each of these factors. Direction of rotation Product variation. Sources of product variation 1. Product in feeder include inconsistent powder density and particle size dis- 2. Scraper tribution. While you may think that density variations 3. Fill cam (partial view) originate with your colleagues in formulation and granu- 4. Weight adjustment cam lation, density can also change on the press, often 5. Ejection cam because of overfilling of the die and re-circulation of the 6. Fill position powder on the tablet press. The particle size distribution 7. Weight adjustment position 8. Pull-down position can change when the product becomes “unblended” dur- 9. Pre-compression ing transfer or because of static electricity. It might also 10. Main compression change because the product can’t withstand the handling and the mechanical stress it undergoes before reaching the tablet press. Head pressure. This factor is related to the amount of Machine condition. The problems caused by a tablet product in the overhead feed system or hopper. The press that is poorly prepared or operated are legion. Look more product present, the greater the head pressure, and at the die table. Have you inspected its runout? The up vice versa. When the pressure varies, so does the weight and down motion under load on a new die table should be of the tablets. within 0.003 inch of the setting. You must also ensure that Hopper level. To keep the head pressure consistent, the pressure rolls and cams are in very good condition. you need to maintain the product in the hopper at a con- Tooling condition. There is quite a bit of information sistent level. Maintaining the level within a narrow range available on tooling, but in a discussion of weight varia- will reduce the potential for weight changes. Every oper- tion, the punch working length is the property that you ator knows that tablets produced at the end of a run must know. Working length is the key factor in how weigh less than those made at the start. That’s because punches affect tablet weight. New tools are made to a the hopper level (and thus head pressure) decreases dur- tolerance of one-thousandth of an inch, which is equal to ing the run. If you determine that variations in the hop- the thickness of one page in this magazine. Make sure the per level are linked to variations in tablet weight, you length of each punch is correct and identical. must monitor the weights more often and adjust your Powder flow and feed-rates. Many of the defects equipment so the level is more consistent. related to powder flow and feed-rates stem from the for- Feeder clearance. Generally speaking, you should set mulation you’re given, not the operation of the tablet the clearance between the feeder and the die table press. Since the focus of this article is resolving problems according to the product’s particle size. The smaller the at the tablet press, I won’t go into the many problems particle size, the smaller the clearance between the feeder that may be related to the granulation process or the for- base and the die table, and vice versa. That’s the general mulation itself except to say that too many fines is bad. I rule, but there’s a big “if” involved here: If the powder is address fines in more detail at the end of the article and waxy or very moist, a feeder that is incorrectly set may in the sidebar on page 42. compact, or “pack” the powder on the die table. In such cases, the only way Figure 2 replace it as needed. to determine the When the blade is best setting is to Removing the feeder from this tablet press reveals segregated powder, in bad condition or experiment with dif- which ultimately leads to weight fluctuations. Running the feeder too fast is set up incorrectly, it ferent clearances. one cause of segregation. won’t scrape the die Feeder speed. table clean, and The feeder delivers you’ll have problems powder from the with weight control. hopper to the die Re-circulation. table, and the rotat- After the scraper ing paddles in the blade levels the feeder are intended powder in the die, it to match the pow- guides the excess der flow rate to the powder into a re- rotational speed of circulation channel. the press. The This allows the feeder can also un- powder to travel on mix blended pow- the turret until it ders, and the pad- returns to the feeder. dles can break If the fill cam is set friable granules and too deep, there may compact highly be “an excess of moist powders. The excess” powder in best strategy is to the re-circulation run the feeder as channel. When that slowly as possible while maintaining proper tablet happens, the powder will not flow well. It may even back weight. Running the feeder too fast can also cause the up, spill, compact, or leak, all of which can reduce yield product to segregate. See Figure 2. and alter the characteristics of the re-circulated powder. Fill cam. The fill cam allows the die cavity to be over- Poor re-circulation produces a powder that is over- filled. The excess is then pushed up and out of the die worked, compacted, unmixed, or otherwise damaged. when it reaches the weight adjustment cam so that the To see what’s happening on the press, use a strobe scraper blade can remove the excess as the die passes by. light. It lets you see how well the product flows, how well Most modern tablet presses include a “pull-down” posi- the scraper blade works, and how well the die and tion after the weight adjustment step. I discuss this fea- punches are functioning. See Figure 3. ture later in the arti- cle. Thin tablets Figure 3 More on weight require a shallow fill variation cam, and thick A strobe light can reveal how well a product flows, how well the scraper blade Those are some tablets need a deep works, and how well the die and punches are functioning. of the machine- fill cam. It’s typically related variables necessary to overfill that can affect tablet the cam by 10 to 30 weight. But what if percent to maintain the weight problem consistent tablet is related to the weights. product, not the Scraper blade machine? In some condition and ad- cases, you’ll be justment. The tempted to return scraper blade is a the problematic wear part. It’s worn product to the gran- by die table rotation ulating department. and product abra- More likely, you’ll sion. The more be asked to consult abrasive the prod- your supervisor. uct, the faster the Operator: So are scraper’s edge will you going to answer wear. So inspect the my question? What blade frequently and do I do? Supervisor: Hmm. Isn’t the next shift going to be here to exhaust the other options. Changing the powder den- soon? Just joking! sity is likely impossible, unless it’s a machine-induced In the real world, we have to solve the problems, not density problem, as described earlier. pass them along to the next shift. The first point to You can increase dwell time to increase hardness, but remember: Change one (and only one!) variable at a longer dwell times typically require you to slow the time. The next step is to define the extent of the prob- machine, and that’s not usually an option. Instead, I rec- lem by checking the tablets closely. Is there a pattern to ommend that you first decrease tablet thickness by adjust- the weight variation among individual tablets? Is the ing main compression. Or, if you are already at the target variation consistent? Does it come and go? Is the trend weight, then decrease the thickness and increase the pres- toward overweight or underweight tablets or does it go sure at pre-compression. If you make that change and both ways? you’re still achieving your target weight—that is, the At some point you might think, “But I’ve got auto- tablet hardness increases and decreases rapidly but the matic weight control on my tablet press! Why is this weights are consistent—then you have what is known as a happening in the first place?” Well, you have to under- dwell-sensitive granulation. Finally, as mentioned earlier, stand that “automatic weight control” works by allowing you must know that the tooling is in good condition. If the tablet press to make weight adjustments based on the diameter of the tooling head flat is inconsistent within variations in compression force. When the compression the set of punches, then hardness will be inconsistent. force is below the limit, an electronic signal tells the To summarize: If you have trouble controlling hard- tablet press to fine-tune the weight adjustment cam to ness, first check for consistent weights. If the weights are increase the fill volume. When the compression force consistent, then check the thickness. If the thickness is increases, another signal tells the tablet press to fine- consistent and on target, then reduce the thickness at tune the weight cam to reduce the volume of fill. That’s pre-compression. Only increase the weight or reduce all weight control is, nothing more. In short, you must machine speed when you have determined that there are make incremental adjustments to the weight cam to no other options. attain accurate volumetric change, which—given a known and fixed product density—relates precisely to A word on particle size gravimetric change. I’m often asked to define the optimum particle size If you’ve gotten this far and the tablet weights still distribution for making the perfect tablet. That’s a tough vary too much, look closely at how well the machine question. A particle size distribution within the right keeps the product in the die before it’s compressed into a range produces a good-looking tablet, but the nature of tablet. Light, fluffy powders may “splash” out of the die, that distribution depends on the tablet size. If the pow- or the centrifugal force of the rotating turret may cause der contained only large particles, like granular sugar, the powder to come out. Either way, the tablet will be you’d be making a porous sugar cube. Conversely, if all underweight. The best defense against splashing is to use the particles were superfine, you’d have other problems the “pull-down” feature offered on most tablet presses with compression. We need a range of particle sizes that nowadays. This feature pulls the lower cam down, allow- is in harmony with the tablet size. ing the column of powder to drop into the die after fill- Generally speaking, the smaller the tablet, the smaller ing , thus preventing under-filling. It can also prevent the the particle size. Likewise, the bigger the tablet, the big- powder from splashing. ger the particle size. Particles smaller than 200 mesh (74 Reducing machine speed is another good strategy. microns) are generally a problem for compression. Naturally, you’d prefer to move the powder through the Particles larger than 18 mesh (1,000 microns) can cause tablet press as fast as possible, but the formulation dic- weight fluctuations and create a textured appearance. tates the speed of the press. I know companies that pur- This is true for the most common sizes of pharmaceutical chased a new press hoping to make their tablets faster, and health-supplement tablets. Tablet shape is also a con- only to find that the formulation couldn’t match the per- sideration. If the tablet has small sharp corners, then the formance of the press. If you want good tablets instead particles must be small enough to flow and fit into those of just fast tablets, you can only run the press as fast as tight corners. However, if you’re making a round or the product will allow. I’ve never seen a formulation that caplet-shaped tablet, larger particles work better. could outrun the machine. Disintegration and dissolution times are generally better for tablets made with a fine dust-like powder than they are Variations in tablet hardness for tablets made with large-particle powders. Finding a Hardness variation is a defect, and hardness varies happy medium—a formulation that disintegrates and dis- according to how well you control tablet weight, pow- solves well and that also compresses well—requires some der density, dwell time, tablet thickness, and the working true formulating skills. I think that formulators too often err length of the tooling. on the fine-particle side of the issue and don’t consider all Increasing the tablet weight can increase the tablet the issues of tablet making. In short, fines affect yields, hardness, but your supervisor may forbid that because it punch lubrication, compressibility, and can cause the tablets “just gives product away.” Instead, you’ll be encouraged to cap, laminate, or show other defects. Fines also increase My gripe with formulators and granulation staff: fines! I wonder if any formulators out that you must press so hard that it But back to my to my real beef: there have ever run a tablet press, could be used as ammo in your There are too many fines every- really run a press. And I’m not talk- shotgun. Hey, now there’s an idea. where. Why do companies spend so ing about a wimpy run that lasts 5 Maybe these formulators could go much time working powders and minutes, either. In fact, I know that into making artillery rounds, and granulating them when they end up no formulators have ever run a maybe they could hire some of on the press as a pile of dust? tablet press under production con- their buddies from the granulation I’d like you formulator and granu- ditions. If they had, I doubt department to go with them. lator guys to get out there and look whether they’d be formulators. By the way, while I’m at it, I’ve at the issues. The fines are every- Having run a press for years, I never, ever met a supervisor who where, and it’s really a problem. think the only folks more mis- knows anything more than how to Think about it: You guys cannot be guided than formulators are people deliver a stack of paperwork. making a good product when 30 to who think they know how to gran- When it comes time to fix a prob- 50 percent of it is dust. I know, the ulate. Maybe we could put these lem, they become politicians: formulators will say that the fines would-be formulators in a room “Well what do you think the prob- help disintegration. And I’ll reply, with the mill operators, throw in a lem is?” they ask. It’s never said, but “Baloney!” The fines are killing the few supervisors, and lock the door. the press operators must be think- press run, they don’t compress well, Then I’d gather the people who ing: “You have got to be kidding! and there is no benefit to fines. You run the tablet press and make some Why does the handbook say I call yourself a formulator, but any- real products. There won’t be any must consult you, the boss, when one—you don’t need an advanced of this superfine stuff that doesn’t you don’t have a clue about what degree—can grind powders into a disintegrate for 3 weeks, the stuff to do?” pile of dust. M.T. tabletting run times Table 1 Michael D. Tousey is and cleaning fre- owner and technical quency. Table 1 re- Excessive fines can services director of DI peats these points. If I were allowed • Remove the oil from punches, leading to tight punches that leave black specks in the tablets Pharma Tech, 152 • Reduce the effectiveness of the formulation’s powdered lubricant, increasing the required just one statement ejection force Wilkinson Drive, on particle size dis- • Decrease yields while increasing the amount of dust collected and the frequency of cleaning Westminster, SC tribution, it would • Cause capping and lamination 29693. Tel. 864 657 be this: Most formu- • Decrease content uniformity and impede product flow lations contain too 5400, fax 864 647 many fines, and by 1155. Website: “most,” I mean about 95 percent of them. If the people www.dipharmatech.com. Tousey has been involved in the responsible for formulation understood compression, pharmaceutical industry since 1973, including work at they would never make a product’s particle smaller than Thomas Engineering, Shaklee, Pennwalt Stokes-Merrill, what’s necessary to achieve the target dissolution rate. If more products had better particle size distribution (fewer and Lakso. He founded his company in 1989. Tousey is a fines), the press would run better and longer with less member of the Editorial Advisory Board of Tablets & cleaning and fewer defects. T&C Capsules.
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