Poor tooling condition can cause many tableting problems, but these problems can be minimized or eliminated by adopting a simple, seven-step tool-care process. The “seven-step process” is a logical, planned, and professional approach to tooling maintenance and storage that has been adopted by many companies around the world as a standard operating procedure.

The seven steps are summarized as follows:

 When tooling is removed from the tablet press, it should be thoroughly cleaned and dried to remove any oil or product residue, especially from difficult-to-reach areas (e.g., inside embossing and keyways). Equipment used for this process could include ultrasonic cleaning and automated washing processes. It is essential, however, that the process does not cause corrosion of the tooling material, and to that end, a corrosion inhibitor should be used.

 Punches and dies should be visually inspected under magnification for signs of damage, wear, or corrosion, and to validate the cleaning process. This assessment will establish if the production process is running well or not. The assessment will also give clues to problems with the tablet press or tooling itself and indicate if any tooling maintenance is required. Typical equipment includes high magnification lenses and microscopes.

 Light surface wear, corrosion, and damage on tooling can be repaired and polished to a useable condition. Worn tips can result in poor quality tablets and inferior embossing definition, which can lead to picking and sticking. Equipment such as a motorized chuck and double-ended polishing motor are used in conjunction with polishing accessories. Repair should be carried out by well-trained and experienced maintenance technicians to ensure that the tooling is not taken out of tolerance limits. Repair should not be carried out on coated tooling as this may remove the coating from the punch.

 Measuring is essential after repair to ensure that crucial tooling dimensions have been maintained within an acceptable working tolerance. The equipment for measuring can range from simple hand-held micrometers, vernier callipers, and height gauges to semiautomatic, computerized, digital-gauging systems. Measuring should be carried out at regular intervals, even if repair has not been necessary, to check for natural wear during the compaction process. The essential measurement is the critical working length of the punch as this controls tablet thickness, weight, and dosage.

 Controlled, light polishing on a frequent basis will ensure that the tools are maintained to a smooth finish, helping to maximize tooling life and reduce problems such as sticking and capping. Remedial, manual polishing can be conducted using double-ended polishing motors with nylon polishing wheels and fine abrasive compounds. A more controlled and consistent process is the automated, drag polishing system, which relies less on the skill and experience of the operator. This also allows for up to 70 punches to be polished in one 20-minute cycle, thus providing efficiency gains. Recleaning after polishing is not required provided that a food-grade polishing media and paste is used during this operation.

 Lubrication is important to protect, preserve, and aid smooth operation of the tooling. A range of oils and greases can be recommended for different applications.

 Tooling storage and transportation should be specifically designed to maximize security and safe handling to minimize damage and deterioration. There are different ways to safely and securely storing tablet tooling; these range from storage cabinets to custom-designed storage containers. Whichever system is adopted, it is important that the tooling is separated to avoid contact and that the tooling condition does not deteriorate during storage.

Application of the seven-step process will have a direct impact on the reduction of many common tablet and tooling problems, thus resulting in a better quality tablet, and can provide direct cost saving for the tablet manufacturer.

For examples of how the seven-step process can be applied to real tooling problems, read the article by Trevor Higgins in the upcoming February 2013 issue of 

Trevor Higgins is a technical expert at I Holland,

Articles

Troubleshooting

Adopting a seven-step process resolves tableting problems.

Improving Tablet-Press Tooling Maintenance and Storage

Cole-Parmer
 Portable freezer offers secure, low-temperature transport

Yokogawa
 Dual bent-tube coriolis meter measures liquid and gas flow at low rates


    Yokogawa’s RotaMass LR is, according to the company, the world’s smallest dual bent-tube coriolis meter, and it is designed for accurate and stable measurement of fluids at low flow rates. The meter measures mass flow of gases or liquids from 0–40 kg/h, with an accuracy of +/- 0.15% for liquids and +/- 0.5% for gases. The dual bent-tube design decouples the core-measuring element from process vibration that can cause fluctuating zero stability and decrease measurement accuracy. It is also insensitive to fluctuations in ambient temperature. Although tubes with a smaller surface area normally make it more difficult to measure temperature, the RotaMass LR solves this problem by using an inline temperature sensor that ensures exact and fast measurements in process temperatures ranging from −50 to +150 °C.

January 2013 Editor's Picks: Products from Cole-Parmer and Yokogawa

Pharmaceutical manufacturers devote considerable time and resources to implement effective cold-chain practices that protect products, especially sensitive biopharmaceuticals, blood products, and vaccines from damage. Although efforts have traditionally focused on frozen (−20 °C) and refrigerated (2–8 °C) products, there is growing attention to controlled room temperature (CRT) products, which require maintenance at 15–25°C to ensure quality and efficacy. Dramatic growth in the number of temperature-sensitive products, as well as evolving regulations worldwide, make it more essential than ever to manage conditions in storage and transit. 

Data loggers, which record conditions the shipment experiences and can quickly indicate if a problem occurred, are increasingly being used to meet this need for tracking and managing conditions. The trend is toward greater scrutiny of the data from each shipment says Andrew J. Mills, CEO, Americas for Intelsius, a DGP Company and supplier of temperature-controlled packaging. With data being more carefully evaluated, there will be “greater pressure on temperature-controlled packaging providers to do a better job of qualifying their solutions against multiple temperature ranges,” he adds.

Ease of use for data loggers is maximized by features like an onboard USB connection. “When plugged in, the logger provides PDF data files,” explains Rich Ellinger, vice-president, Life Sciences at PakSense, the maker of a label-like data logger (BIOmed XpressPDF Temperature Monitoring Label). “No additional infrastructure is needed.”

With wireless technology, a container doesn’t even have to be opened to access temperature data. Keeping the shipper closed not only helps maintain the environment around the payload, but also means, “there’s no need to change supply-chain practices to collect information,” explains Kevin Payne, senior director of marketing at Intelleflex, a provider of radio-frequency identification (RFID) tags and related software for temperature monitoring. Data can be read or written to a Class 3 battery-assisted passive RFID tag at distances up to 300 feet. This stronger penetration power allows readability through ice and insulation, for example. The credit-card-size tag, which measures about 0.25-inch thick, will gain functionality in 2013 with the addition of humidity and light-monitoring features (TMT-8500 temperature monitoring tag, Intelleflex). “Light monitoring is important because recipients can tell if the box has been opened during its travels,” explains Payne. 

Interest in RFID-based monitors is increasing, according to Tom Dolan, director of sales at RURO, a supplier of turnkey RFID systems. Since hundreds or even thousands of RFID tags can be scanned at the same time, the technology offers potential for high-speed automated data collection not possible with traditional barcodes. In addition, Dolan says, RFID “costs have come down, and there are more vendors in the market.” Furthermore, performance improvements allow RFID tags to work reliably despite metal interference and other challenging conditions like cryo environments. 

For more about this topic, read Hallie Forcinio’s cover story, “Packaging Innovations Aid Cold-Chain Efficiency” in the upcoming February 2013 issue of 

Hallie Forcinio is Pharmaceutical Technology's packaging editor, 

Packaging

Advances in data loggers and radio-frequency identification tags help meet the increasing need for managing the pharmaceutical cold chain.

Logging the Cold Chain

Micronization, which reduces particles down to the micrometer or, in some cases, nanometer (1/1000 of a micrometer) size, can be used to improve the bioavailability of poorly soluble APIs by increasing particle surface area and accelerating dissolution rates. Micronization can also be used to improve formulation homogeneity and control particle size. A wide range of drug types, including solid dosage, injectable, ocular, and inhaled products, can benefit from micronization. Micronization is most often used to describe processes that reduce particle size by using fluid energy, such as a jet mill, rather than by mechanical means.  Mechanical particle-size reduction using a bead mill, however, can also be used to obtain micrometer- and nanometer-sized particles.

Jet milling
 Jet milling does not use mechanical components, but instead uses pressurized gas to create high particle velocity and high-energy impact between particles. After exiting the jet-mill chamber, the process gas is separated from the solid particles with a cyclone filter. Compared with mechanical milling, jet milling reduces metal contamination and, because process temperature is relatively constant, can be used for heat-sensitive products, explained Giovanni Gianola, managing director of FPS Food and Pharma Systems (FPS) at a recent industry seminar (1). Jet milling, however, has relatively low productivity, large equipment size, and high process-gas flow requirements, therefore requiring high process knowledge to optimize its use. Micronization using spiral jet milling has been a poorly understood “black box” process, but process understanding is growing as pharmaceutical companies work together with equipment manufacturers, said Gianola. Parameters include equipment geometry, temperature, and powder characteristics (e.g., humidity, density, impurities, and incoming particle size distribution) as well as the variables of pressure and solid-feed rate (i.e., specific energy). Improved understanding can lead to improvements in productivity, particle size distribution, and gas consumption, for example. Temperature control for cryogenic applications is also being investigated and adopted, says Gianola.

The desired particle size depends on the solid-dosage requirements, notes Brian List, sales and marketing manager at the Jet Pulverizer Company, with typical API particle sizes in the 2–5 micrometer range. The minimum particle size that can be obtained using a jet mill depends on the inner friability of the material, explains List. Many APIs are synthesized or precipitated at the nanometer-scale but are agglomerated, and a jet mill can also be used to deagglomerate these APIs down to their original nanometer base-particle size.

Jet milling under containment
 Because of the prevalence of potent compounds, micronization is increasingly being performed under isolation. A mill can be enclosed inside a barrier isolator for processing highly potent drugs. In addition, jet mills can be operated in sterile conditions by integrating the mill in an isolator or a restricted access barrier system (RABS) as needed, notes Gianola.

Some products are not considered potent, yet still require containment because of environmental, health, and safety (EHS) concerns as a result of the small particles created after the micronization process, notes Mike McDougal, director of sales and marketing at Micron Technologies, which provides micronization and analytical services to the pharmaceutical industry. The company has custom-designed containment systems that provide the ability to jet mill high volumes of product under containment.

Jet mills can be designed with tool-less, sanitary-clamp connections to allow easy assembly and disassembly inside a glovebox. A recently introduced spiral jet mill was simplified with fewer parts for even easier assembly, says List (Pharma-Master, The Jet Pulverizer Company). This mill, which has been awarded USDA acceptance, also minimizes hang-up points to improve cleanability and includes a one-piece, weldless feed funnel injector.

Bead milling
 There is increasing interest in bead milling as a micronization method for pharmaceuticals, says Randy Smith, president of Netzsch Premier Technologies, a US-based company in the Netzsch Group’s Grinding and Dispersing business unit. A bead mill uses wet mechanical milling to obtain nanoscale particles as small as 200–400 nm in what can be called micronization, or perhaps more accurately named “nanonization” because it refers to nanometer scale, says Smith. In an agitator bead mill, grinding beads and agitating elements are used to reduce the API particle size through impact, and shear. Product is separated from the grinding media at the outlet. Process parameters include the formulation (e.g., product viscosity, percent solids, additives to prevent reagglomeration), bead density, bead size, bead-filling ratio, stirrer-shaft speed, and flow rate, explained Smith in a presentation at a recent industry seminar (2). For a particular formulation, the process parameters and the material of construction of the bead mill must be optimized so that there is enough force generated for micronization but not excess force that might change the particles’ aspect ratio or lead to preventable risk of contamination, explained Smith.

Because bead milling is a wet process, it avoids any problems related to dust.  If containment is needed, the batch-mixing tank can be placed in an isolator, and the mixture can be pumped to the bead mill, which is outside the isolator but is itself a closed system, explains Smith.

G. Gianola, “Micronization Systems—Innovative Equipment Design and Applications,” presentation at Advances in Pharmaceutical Processing (Somerset, NJ, 2012).

R. Smith, “Micronization of Active Pharmaceutical Ingredients to Nanometer Scale,” presentation at Advances in Pharmaceutical Processing (Somerset, NJ, 2012).

Production Trends

Micronization can be performed with a jet mill or bead mill.

Equipment and Processing Report-01-16-2013

Improving Tablet-Press Tooling Maintenance and Storage

January 2013 Editor's Picks: Products from Cole-Parmer and Yokogawa

Logging the Cold Chain

Using Micronization to Reduce API Particle Size