The technique of continuous coating has undergone great change since it was introduced to the pharmaceutical industry more than a decade ago, and its benefits have multiplied. At first, the method enhanced throughput and increased operational efficiencies. Manufacturers now use continuous coating to optimize process robustness and maximize the agility of manufacturing technology.

The first continuous coaters used in the pharmaceutical industry were adapted from seed-coating machines developed by Coating Machinery System  (CMS, Huxley, IA). The technology was designed to increase the size of seeds so that automated planters could plant them. The original design consisted of two stacked, perforated cylinders and multiple spray guns. Thomas Engineering (Hoffman Estates, IL) was the first company to develop a continuous coater designed specifically for the pharmaceutical industry. Shortly after Thomas introduced its coater, Vector (Marion, IA) acquired the CMS system and redesigned it for the pharmaceutical industry. The Thomas and Vector units have a throughput of roughly 200–800 kg/h. 

O’Hara Technologies (Richmond Hill, Canada) entered the market later with a design similar to those of Thomas and Vector, but with a throughput of 700–2000 kg/h. All of these coaters share the same basic design. Tablets are fed into one end of a long, continuous, perforated, rotating cylinder. Next, they are conveyed through the cylinder by baffles, coated by multiple spray heads, and dried using conditioned air flow. Finally, the tablets are discharged from the unit. 

Niro’s (Columbia, MD) “Supercell” machine represents a recent advancement in continuous coating. The unit is designed as a continuous cell coater and is similar in appearance to a Wurster coater. Tablets are loaded into a feed hopper. A subset of tablets (30–120 g) is fed into the cell by a vibrating loss-on-weight feeder. The unit coats this subset of tablets in 1–3 min. The Supercell coater provides a throughput of 1–4 kg/h. 

The reasons to use continuous coating technology vary depending on the drug product’s phase of development. Clinical-supplies manufacturing typically requires small batches of many doses to meet trial needs and fulfill the clinical-study design. In addition, the product must be supplied quickly to accommodate the clinical-trial’s schedule. The advent of small-scale continuous coaters allows manufacturers to ensure that clinical batches match the studies’ needs. Manufacturers can thus reduce the waste that results from overmanufacturing. 

In commercial manufacturing, the benefits of continuous coating technology are predominantly cost and efficiency. High throughput, large yield, and lower capital and facility expenditures are the primary advantages. Continuous coating technology has the additional advantage of featuring a smaller footprint than traditional units. 

On the other hand, continuous coating does entail some startup and end-of-batch waste, which may limit the technique’s appeal in terms of yield. Process analytical technology (PAT), however, may reduce yield losses and permit an accurate, real-time assessment of coating amount and coating uniformity. The US Food and Drug Administration’s 

A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance

 opened the doors for pharmaceutical companies to develop and use new processing technologies. The guidance aims to help pharmaceutical manufacturers by “providing a set of scientific principles and tools supporting innovation and a strategy for regulatory implementation that will accommodate innovation.” 

The adoption of continuous coating technology has so far been limited, perhaps by the historical definition of a batch in the pharmaceutical industry and by the industry’s aversion to bringing new manufacturing approaches to regulators’ attention. With the advent of the PAT guidance and advancement of PAT technologies, pharmaceutical manufacturers will be able to take advantage of the benefits of continuous coating and still meet the need for quality.

Ruey-ching (Richard) Hwang, PhD, is a senior director of pharmaceutical sciences at Pfizer and a member of 

’s editorial advisory board. Robert Noack is a senior principal scientist at Pfizer. 

Articles

In the Mixer

The technique of continuous coating has undergone great change since it was introduced to the pharmaceutical industry more than a decade ago, and its benefits have multiplied.

Trends and Innovations in Continuous Coating

In light of the rising price of stainless steel components and facility construction, pharmaceutical companies are increasingly using disposable components and systems in their manufacturing processes. Ahmad Shahidi, a senior technical consultant at Parsons (Pasadena, CA), notes that manufacturers can save as much as 25% in capital costs by using single-use systems. But in this era of dawning ecoconsciousness it has become important to ask whether disposable systems also bring environmental benefits.

Absolutely, Shahidi says. He notes that disposable components reduce the amount of liquid waste a pharmaceutical facility generates by as much as 70–90%. Most of the purified water in a typical pharmaceutical manufacturing facility is used for cleaning purposes, he explains, which then leaves the facility as waste that must be treated and cooled, as does the used cleaning solution. Because single-use components are presterilized, they eliminate the need for cleaning and sterilization, which, in turn, reduces the consumption of water, clean steam, and cleaning-solution, Shahidi notes. “That’s the tremendous advantage of single-use equipment,” he says.

Geoffrey Hodge, vice-president of process development and technology at Xcellerex (Marlborough, MA), raises a similar point. Using disposable components reduces the need for water for injection (WFI), he remarks, because manufacturers don’t need to produce clean steam to sterilize the products. “The opportunity to reduce water consumption … is one of the factors driving the interest in disposable components,” Hodge says.

Single-use systems can also lower the amount of clean, compressed air that facilities use. Cleaning-in-place systems represent a large proportion of compressed-air consumption, Shahidi observes. Operators blow residual cleaning solution out of their systems with compressed air. “Obviously, if you don’t perform cleaning, you don’t use that proportion of compressed air,” comments Shahidi.

Manufacturers also use compressed air during equipment sterilization. After equipment has been sterilized, it is hot and must be cooled. Operators use compressed air to break the vacuum and cool the equipment. But single-use systems don’t need to be sterilized in place. “Compressed-air consumption is reduced by, say 50–70%” when you use disposable components, Shahidi estimates.

On the other hand, using disposable components generates more solid waste. Processing this waste-typically by incineration-could have negative ramifications for the environment. “The effect of incineration on air quality must be balanced against the energy savings and the significant decrease in wastewater discharge that results from eliminating cleaning and sterilization operations,” Hodge says.

Although Shahidi agrees that the increase in solid waste generated by single-use components is a drawback, he argues that the increase is “marginal” compared with the “substantial decrease in the liquid waste generated.” In addition, Shahidi is quick to point out that “you can recycle the components easily,” which could lessen their environmental impact. In conclusion, disposable components do not have any significant drawback from an environmental standpoint, Shahidi asserts.

Single-use systems would not be enjoying their current high level of popularity if manufacturers believed that the products were more expensive than they were worth. A similar cost–benefit analysis could be used to assess whether disposable technologies are environmentally beneficial. If single-use systems promote a healthy environment, they protect human health. And human health is pharmaceutical companies’ main concern, after all. 

Production Lines

In light of the rising price of stainless steel components and facility construction, pharmaceutical companies are increasingly using disposable components and systems in their manufacturing processes.

Are Disposable Components a Green Solution?

 
 Parker-TexLoc’s (Fort Worth, TX) fluoropolymer FEP and PFA tubing are leak-free, low-maintenance alternatives to metallic tubing. They can be formed and welded into heat-exchanger transport lines that offer bacteria-free transport of deionized water and other corrosive media. The tubing’s high lubricity “prevents contamination because nothing sticks to it,” according to Janine Kruit, a marketing professional at Parker-TexLoc. The high lubricity also reduces downtime for cleaning and routine maintenance.

FEP and PFA are melts, and “you don’t have to add lubrication to them to extrude them,” Kruit says. This property makes them cleaner materials compared with paste-based polymers. The materials also have high chemical resistance that stops residue from collecting in the tubing.

The products absorb less than 0.01% moisture absorption and operate in temperatures as high as 260 °C. 

 
 Automation Products Group (APG, Logan, UT) introduced its “LPU-2428” loop-powered ultrasonic level sensor. Jacob Bingham, APG’s application engineer for ultrasonics, level, and flow, notes that many comparable sensors simply provide a distance reading. The LPU-2428 sensor’s programming software offers distance and level readings and generates data reports. In addition, the “unit uses a distance reading to perform weir and flume calculations,” he explains. The device’s microprocessor control internally performs volume, flow, and totalization calculations.

Users can select flow-rate units of per second, per minute, per hour, or per day. Standard volume units include cubic feet, millions of cubic feet, gallons, cubic meters, and liters.

Bingham adds that the sensor’s autosense mode adjusts its sensitivity and pulses to get accurate data. The unit also features a manual sensing mode.

Featured products from this issue of Equipment & Processing Report

Equipment and Processing Report-01-25-2008

Trends and Innovations in Continuous Coating

Are Disposable Components a Green Solution?

January 2008 Editor’s Picks