欧哈勒OHara连续式包衣机性能及优势

tablet coatingAdvantages of continuous pharmaceutical tablet coating James MarjeramO’Hara TechnologiesMany tablet manufacturers have become interested in continuous tablet coating to replace or supplement traditional batch-style tablet coating. This article discusses the reasons for their interest and weighs the advantages and disadvantages. It also discussesthe importance of tablet movement through continuous coaters.or many decades, pharmaceutical manufacturers have relied on batch operations, so why would they now con-sider continuous tablet coating or other continuous oper-ations? There are several reasons:• Potential to employ on-line or at-line process analyt-ical technology to reduce the need for laboratory-based quality control and the associated hold points lab-based testing requires;• Faster, easier, and less expensive scale-up from R&D to pilot-scale operation and from pilot-scale opera-tion to production. All scale-up can be done in simi-lar machines or drum sizes;• Ability to vary batch sizes according to product requirements and demand. It’s possible to coat 150-to 30,000-kilogram batches in a single machine;• I ncreased equipment utilization and thus less down-time because the equipment spends more time coat-ing and less time in unproductive process steps; and • Contained processes—from start to finish—are benefi-cial for potent products. They reduce operator expo-sure to the API and other dusts and minimize cleaning.Creation of a fully continuous, fully automated solid dosage tablet manufacturing line is, some people say, theFHoly Grail of the pharmaceutical industry. Unlike that legendary chalice, however, continuous coating appears to be within our grasp, and part of it might look some-thing like the diagram in Figure 1. Listed below are yet more advantages of continuous coating and some of the economic benefits they entail:• Less product loss, less product damage, and higher quality. The improvements stem from less product handling, shorter residence times, and shallower tablet beds compared to batch coaters;• Less variability because the process is more con-trolled and repeatable;• Lower capital cost and higher equipment utilization, which means lower capital expenditures when build-ing the facility;• Less labor and thus lower labor costs;• Smaller facilities because fewer machines are needed;• Lower utility costs because fewer machines are needed; and• Faster processing, shorter storage periods, less wait-ing, and faster material transport.Table 1 provides cost estimates of installing and oper-ating a continuous coating process.Evolution of continuous coatingContinuous film coating is not a new technology. It has been used in the agricultural seed industry for many years. In fact, the polymers used to coat seeds are similar to the polymers used to coat tablets; both are based on hydroxypropyl methylcellulose. Thus it is no surprise that seed-coating technology evolved to apply film coat-ings to tablets.The first companies to embrace continuous tablet coating were manufacturers of dietary supplements because, until recently, they were unencumbered by Good Manufacturing Practice (GMP). These companies were thus free to experiment and challenge how things were done, to develop methods that coated tablets with less expense and gave better results. There was no fear or risk of repercussions from the regulators. Indeed, dietary-supplement manufacturers have benefitted from the tech-nology for many years, especially in the USA, where vol-umes are high.In the pharmaceutical industry, however, adoption of the technology stalled due to regulatory concerns, and many manufacturers remain reluctant for that very rea-son. But in the last few years, the slow economy and steadily rising costs to operate batch coaters (and other batch operations) spurred US pharmaceutical manufac-turers to seek cost reductions. Continuous coating—and continuous processing in general—offered a clear oppor-tunity for relief.First, however, continuous coaters needed to change in two ways: better cleanability and lower throughput vol-umes. In the seed industry, cleanability wasn’t an issue, so there was no need for GMP compliance or the addition of wash-in-place (WIP) or clean-in-place (CIP) systems. Both were mandatory in order for the pharmaceutical industry to adopt continuous processing. A reduction in throughput was also needed, since coating seeds is a much higher-volume operation than coating pharmaceu-tical tablets.Other features also needed improvement, including spray nozzles that clogged, tough-to-clean industrial drum drives that used transmission belts, product wastageat the beginning and end of batch runs, hard-to-clean air plenums, and process cabinets fastened with screws instead of being fully welded. In the last 5 years these problems have been resolved, and coaters for pharmaceu-tical use may now include• Anti-bearding spray nozzles;• Friction-drive drum rotation mechanisms;• No-waste start-up and shut-down;• GMP-compliant cabinets and integrated air plenums;• Fully welded and polished process cabinets with inflatable air seals in some places;• Integration of WIP/CIP systems;• Control systems that automate recipe setups and comply with 21 CFR Part 11; and• Tablet loading and unloading systems.Batch and continuous coaters: Similarities and differencesA continuous coater is similar yet different from a tra-ditional pharmaceutical batch coater. Both machines use similar rotating perforated drums that are stretched in the axial direction, parallel to the spray nozzle array. But determining how much coating is applied to the tablets—average weight gain—must be figured differently, as shown below.Batch coating:WG ϭSR ϫSC ϫCE ϫCT ϬBWContinuous coating:WG ϭSR ϫSC ϫCE ϬTRwhereWGϭaverage weight gain of tabletsSRϭsolution spray rateSCϭpercentage of solids in solutionCEϭcoating efficiency correction factorCTϭcoating timeBWϭstarting batch weightTRϭtablet feed rate.In operation, tablets enter a continuous coater at a controlled rate and a highly precise metering system con-trols the application of coating, just as is done in batch coaters. But while tablets in a traditional batch coater require radial and axial mixing to achieve weight gain uniformity, tablets in a continuous coater mix only radi-ally. Indeed, axial mixing in a continuous process would imperil product uniformity because a continuous coater provides first-in, first-out flow. Only by maintaining a consistent residence time can a continuous coater spray equal amounts of solution on the tablets and, conse-quently, achieve uniform weight gain.Axial movementWhile axial mixing is unwanted in continuous coaters, axial movement is a must, and two methods are com-monly used to achieve it. In the first method, the drum has baffles or vanes similar to those used in a batch coater. The baffles are oriented in one direction and at a consistent angle along the drum’s axial length. As the drum turns, the tablets deflect off the baffles, and the faster the drum rotates, the faster the tablets pass through the coater. The second method relies on natural migra-tion, which means the more tablets you put into the coater, the more the tablets get pushed through the drum. In the second method, anti-slide ribs are used instead of baffles. These run in parallel along the length of the drum to provide traction to the tablets, but they do not promote axial mixing or movement.Both methods come with restrictions and disadvan-tages. The first method, in which axial movement depends on the drum’s rotational speed, is good because it controls tablet movement regardless of the tablet in-feed rate. However, that can create process restrictions on what type of tablets can be handled and what throughput rate can be achieved. Furthermore, it’s possi-ble that the baffles will be coated in addition to or instead of the tablets, which makes the machine more difficult to clean and maintain than coaters without baf-fles. The first method also limits the nozzle-to-bed dis-tance because of the clearance required for the baffles to pass behind the spray gun nozzle array.A continuous tablet coater for pharmaceutical useAxial movement of tablets through a continuous coaterThe second method is good because it simplifies the interior of the drum, making it more cleanable, and axial movement of the tablets doesn’t depend on the drum’s rotational speed. The disadvantage is that axial move-ment and spreading of the tablets must be understood and controlled. The net average movement of tablets axi-ally through the drum—which depends on the tablet in-feed rate—must be significantly greater than the ability of the tablets to spread upstream. If the tablets spread upstream, there could be (theoretically) tablets that never leave the drum. That would be a problem.One study on the topic showed that the tablet in-feedrate and the tablet bed depth can control the net tablet flow and tablet spreading. Together, those two parame-ters control tablet residence time, which relates directly to the time that the tablets spend in front of the spray nozzle array. In the study, video recognition equipment tracked marker tablets as they moved through the drum.(See photo.) After conducting several runs at different throughputs and bed depths, a relationship was estab-lished: The higher the in-feed rate and the lower the bed depth, the more quickly the tablets moved axially (in the positive direction) through the drum. That is the best relationship for achieving uniform axial tablet flow. To understand the relationship, envision salmon swimming upstream in a slow moving river (easy) compared to swimming in a fast moving stream (difficult). And if the stream’s current is swift enough, the fish will not be ableto move up it at all. Figure 2 illustrates the relationship between axial flow uniformity, bed depth, and through-put rate.Once the tablets leave the continuous coater, they can be polished (with or without wax) in a continuous opera-tion, allowed to cool if necessary, and then elevated and discharged into a container. Or they could be conveyed directly to a packaging area.T&CFurther readingFor more information about continuous film coating,see “Continuous film coating processes: A review” by Stuart Porter, which appears the April 2007 issue.James Marjeram is sales manager and head of the product inno-vation team at O’Hara T echnologies, 20 Kinnear Court, Rich-mond Hill, ON, L4B 1K8, Canada. Tel. 905 707 3286, fax 905 763 6749. Website: . Marjeram is an electro-mechanical engineering technologist. He has worked in the automotive and pharmaceutical industries and has been employed by O’Hara in sales and engineering since 1988. He holds several patents and has patents pending on innovations related to continuous coating.0.180.150.120.090.0965.6255.254.8754.560075090010501,200Feed rate (kg/hr)S D /R e vBed depth (inches)Standard deviation per revolution (SD/Rev)0.21370.0492SettingsTilt ϭ1.50 inches from level at discharge Automazation ϭ0.50 barAdding marker tablets allows researchers to identify tablet flow patternsand track residence time in continuous coaters.。