BinMaster Level Controls 
 Probes enable delayed notification


 The PROCAP I and PROCAP II capacitance probes from BinMaster Level Controls (Lincoln, NE) perform high- and low-level detection in bins, tanks, and hoppers. The probes can send immediate alerts when they detect a covered state (e.g., to shut off a filling process). Users also can program the probes to send alerts after a delay of as long as 30 s. Operators can apply the immediate and delayed alerts to covered and uncovered conditions.

The PROCAP I and PROCAP II capacitance probes operate at a frequency of 6 KHz and do not interfere with two-way radios or other equipment operating in the radio spectrum. A light-emitting diode indicates each sensor’s status. The units’ PRO-Shield feature compensates for material buildup on the sensing probes and is designed to ensure accurate level detection in dusty, sticky, or clinging materials. The devices are appropriate for various solid, liquid, and slurry materials. 

Kason 
 Sanitary sifter provides easy disassembly


Kason’s (Millburn, NJ) Ultra Sanitary Mini Centri-Sifter product performs fine-mesh screening to a particle size of 25 µm. The sifter has a small footprint and is suitable for difficult-to-screen powders. An operator can remove the device's cylindrical screen–spout assembly and feed screw–paddle assembly by adjusting three hand knobs. The screening chamber can be removed by adjusting one bolt, and the entire unit can be disassembled for sanitization in less than three minutes.

The sifter discharges correctly sized material through an outlet into a storage vessel or processing equipment. Oversized particles exit through the end of the screen cylinder and fall through a second outlet to be discarded or reprocessed. The machine’s dust-tight, sanitary design complies with current good manufacturing practice, according to Henry Alamzad, Kason’s president. Operators can sterilize the sifter manually or in an autoclave. Cylindrical screens are available in woven nylon, monofilament, wire mesh stainless steel, perforated plate, and stainless steel wedge wire.

Articles

PharmTech's monthly newsletter, Equipment and Processing Report, reviews the Editor's Picks for the June 2010 edition from BinMaster and Kason.

June 2010 Editor's Picks: Products from BinMaster and Kason

The pharmaceutical market is changing rapidly because of recent trends such as increasing generic-drug competition, decreasing patient subpopulations, variable product mixes and batch sizes, and the growing role of contract manufacturers. Drugmakers are forced to respond faster than ever to these market influences. Producers of solid dosage forms are looking toward flexible manufacturing strategies to help them remain competitive and profitable. 

Flexibility in manufacturing means, in part, that operators can adapt equipment readily to frequently changing manufacturing requirements. An investment in flexible technology buys a degree of protection against an uncertain future.

Flexibility in tablet coating is achieved when the equipment accommodates the widest possible range of product-load conditions and is versatile enough to handle the gamut of coating processes (i.e., conventional film, functional, modified release, and active-drug layering).

Coaters generally accommodate a specified maximum drum charge of fully coated tablets, which often is referred to as the 

 The key to achieving flexibility, however, is the coater’s ability to coat much smaller volumes or 

 The relationship between brim volume and the allowable minimum charge of cores is the 

 For example, a coater that accommodates a brim volume of 200 L and successfully coats a charge of 50 L is said to have a 25% turndown. A high degree of manufacturing flexibility can be achieved if the coater is equipped with certain features to provide broad volumetric turndown and accommodate the associated range of tablet-bed configurations. 

One factor that influences turndown is the 

 the distance between the spray gun and the bed surface. Adjusting the GTB distance and the angle of spray relative to the bed surface help coaters accommodate the desired range of drum charges.

A drum-charge volume may be defined to minimize the effects of mass on tablet abrasion and erosion. It may also be defined when a lot is divided into several equal charge volumes according to the capacities of upstream equipment. In many processes, the GTB distance and angle remain fixed throughout the entire process. But when the weight gain on the product is high (i.e., more than 20%), operators may need to reposition the gun-support hardware at predetermined intervals during the process as the bed height grows and the GTB distance shrinks. 

To provide flexibility, suppliers offer three-axis, indexed positioning mechanisms that typically feature components with drilled holes and alphanumeric match marks. Quick-release pins hold the gun support in position once the desired orientation has been achieved. Adjustments should be easy to make, ideally without tools, and repeatable.

Another factor that affects turndown is the choice of mixing baffles. Having one or more sets of interchangeable baffles with alternate profiles may be desirable. Low profiles may be used when coating shallow beds, and high profiles when coating deep beds. Submerging the baffles in the bed during coating enhances mixing and helps prevent their direct exposure to the spray, which leads to residue buildup. Interchangeable baffles with different sweep angles and height profiles help operators select a profile to achieve good mixing of friable tablets when the drum speed cannot be increased.

When coating shallow drum charges, operators should match the exhaust-air path through the tablet bed to the bed height. When coating shallow beds, it is desirable to block off the upper portion of the mating exhaust-plenum opening to direct air through the bed, not around it. A range of plate sizes is useful in sizing the plenum opening from the top down to match the bed height.

Factors other than the coater also affect flexibility. Turndown of the process air-handling system (i.e., the difference between the maximum and minimum amounts of drying energy that can be supplied to the coater) helps achieve the widest practical range of airflow rate, temperature, and dewpoint conditions needed. Turndown of the solution-delivery system (i.e., the difference between the maximum and minimum solution-delivery rates), along with alternate pump types and interchangeable spray-nozzle setups of various sizes, helps provide flexibility in handling a wide range of solution properties and flow rates.

Flexibility in manufacturing coated tablets is an essential tool that helps drugmakers confront rapid market changes. Coating systems must be readily adaptable to coat today’s evolving array of products under optimal process conditions. A lack of flexibility would place unacceptable limits on products and processes and require manufacturers to accommodate the coater’s limitations.

Edward S. Novit is a former coating-systems product manager at Thomas Engineering, tel. 847.691.2942, 

In the Mixer

Producers of solid dosage forms are looking toward flexible manufacturing strategies to help them remain competitive and profitable.

Turndown Helps Achieve Flexibility in Tablet Coating

In the 1960s, at about the same time that exposure to gamma rays turned diffident physicist Dr. Bruce Banner into the Hulk, pharmaceutical companies began adopting gamma irradiation as a sterilization technique. Over time, new methods of radiation sterilization have emerged. Electron-beam sterilization, one of these new methods, is becoming increasingly popular among drugmakers.

Electron-beam, or e-beam, sterilization works much the same way that a tube television does. A device called an electron-beam accelerator produces electrons in a vacuum. Rather than being stopped by a TV screen, the electrons travel in a beam through an output window to the product. The radiation breaks down the DNA of the microbes with which it comes into contact, thus making them unable to replicate. A dose of about 25 kGy can yield a 7-log decrease in the amount of microorganisms on a surface (1).

Companies have installed e-beam sterilizers on line to treat products that travel along a conveyor belt. The technique aids the transfer of materials such as plastics and lightweight glass components into isolators, restricted-access barrier systems, or aseptic filling lines. Drugmakers previously did not have an effective way to introduce these materials into their aseptic environments. Instead, the industry either avoided them entirely or sanitized them. Operators used to wipe down glass-syringe tubs manually before transferring them into the aseptic fill room or isolator, a solution that many considered unsatisfactory. E-beam sterilization allows companies to use more plastics and to replace many sanitization applications.

Some manufacturers use e-beams for terminal sterilization, although the method is not common in this function. In the appropriate applications, e-beams also could replace other sterilization methods. For example, companies could use e-beams instead of gas to sterilize the exterior of any internally sterile packaged material, says Jim Agalloco, president of Agalloco and Associates, and a member of 

E-beam sterilization has many benefits for pharmaceutical companies. Unlike methods such as steam-in-place, e-beam sterilization requires no preparation and no poststerilization steps. The process is extremely rapid. “It’s literally like turning the TV on, exposing the item, and turning the TV off,” says Agalloco. E-beam sterilization is quick enough to enable production processes to run at a semicontinuous or continuous mode.

The technique has practical benefits at the plant level, too. Operators might appreciate the fact that e-beam accelerators incorporate a lot of shielding, are quite safe to use, and require little training. Plant managers might be pleased to know that e-beam sterilization can be considered a green technique because it does not require chemicals or water. The equipment uses little electricity and sometimes can cut utility costs by about 80% (2). In addition, e-beam accelerators can be fully integrated into a production process and are easy to validate.

Radiation-based sterilization has certain drawbacks, though, and e-beam sterilization is no exception. The technique damages particular materials such as plastics, but the degradation is not immediately apparent. It could take months for the material to break down, possibly because the free radicals that the process creates remain active during this time. Unfortunately, manufacturers cannot perform accelerated stability tests to determine whether e-beam sterilization is appropriate for a given substance.

E-beam sterilization can present its own challenges as well. Certain materials undergo a color change during the process. Although the change may not be clinically significant, it could raise aesthetic concerns or inspire doubt in patients’ minds. In addition, electrons sometimes strike oxygen molecules and create ozone within a container, which could pose problems for the drug product.

Manufacturers must keep in mind the limitations that e-beam sterilization imposes. For one, the technique requires a small target and is ineffective against large targets such as pallets. And because e-beams are not as powerful as gamma radiation, companies must restrict their use to materials that are easy to penetrate such as plastics and thin glass. Metals and powdered substances are harder to penetrate, and thus more difficult to sterilize effectively with e-beams, says Agalloco.

In recent years, e-beam sterilization has quickly gained favor in the pharmaceutical industry, despite its limitations. At first, radiation was considered the province of experts, and drugmakers shied away from the e-beam technique for a long time. It did not help that early e-beam systems were costly and could be a story and a half tall. As the technology evolved, the machines shrank, and the equipment became more affordable, e-beam sterilization became much more attractive to pharmaceutical companies, says Agalloco. 

Even as the drug industry begins to embrace e-beam technology, observers have seen early signs that another form of radiation sterilization could have pharmaceutical applications. X-ray technology has been improving, and may now be at the point where e-beam was 15 years ago, says Agalloco. X-ray sterilization works by the same principle as e-beams, but uses more powerful radiation that penetrates materials better. Medical-device manufacturers now use X-rays to sterilize large targets such as pallets, and the process operates more quickly than the e-beam technique. On the other hand, X-rays potentially could cause more degradation and increase concerns about worker safety.

Although each method has its drawbacks, the pharmaceutical industry has discovered appropriate applications for several sterilization techniques. The newfound popularity of e-beams and the potential growth of X-rays show that technological developments continue to expand drugmakers’ options for radiation sterilization. 


1. P. Fontcuberta, ISPE Washington Conference (Washington, D.C., 2009).
2. D. Icke, Pack Expo (Chicago, 2008).

Production Lines

Electron-beam sterilization, a new method of radiation sterilization, is becoming increasingly popular among drugmakers.

Equipment and Processing Report-06-16-2010

June 2010 Editor's Picks: Products from BinMaster and Kason

Turndown Helps Achieve Flexibility in Tablet Coating

New Waves of Radiation Sterilization