Issue link: http://www.e-digitaleditions.com/i/626800
! !/ &/#'*'/, !!! !!! !! !!!! ! ! ########## #####!###### #"######### ## #"#######O#60## ## ##### # " ))/+(/"%/"%/ "%)" /"+)/"+%/$%"+)(/(%,(/ /"-/ -/ /$/."+/-)/."+%/$(+/ (/ Challenges of two-piece capsules Every dosage form has disadvantages, and for gelatin two-piece capsules they include the possibility of fills that are incompatible with gelatin. Fills that steal moisture from the capsule shell, for example, could lead to brittle or bro- ken capsules. That's why determining excipient compatibil- ity is paramount: You must identify which excipients work well with both the fill and capsule material to get the desired result. Furthermore, liquid fills reduce the volume available within the two-piece capsule shell because the capsule body cannot be overfilled (as it can with powders) without spilling fill onto the machine, where's it wasted. The practical fill limit for liquids is 90 percent of the capsule's normal body volume. Another drawback: Liquid-filled two-piece cap- sules must be sealed, an extra step compared to softgels. However, if the fill turns solid or semi-solid after it's encap- sulated—because it cools, is thixotropic, or reacts in some other way—leakage may not be an issue. Low-viscosity fills, however, are prone to leakage and the capsules that contain them must be sealed. The ideal viscosity range of fills is 100 to 1,000 centipoise. Anything thicker is difficult to encapsulate. Challenges of softgels While softgels appeal to patients and consumers, there are challenges in developing and manufacturing them, espe- cially if the fill material reacts poorly to high temperatures and humidity. It's also difficult to fill anything but the sim- plest oils into softgels made from a vegetable-gelatin blend, and all-vegetable softgel shells are not as strong as those made from gelatin. Manufacturing softgels also requires a large space and a variety of special equipment, which entails a big capital investment. That prompts most companies to outsource softgel manufacturing. The process also requires special expertise and experience, and that too weighs in favor of outsourcing [2]. Manufacturing softgels is also slower than filling two-piece capsules. Depending on the machinery and the formulation, it could take 30 to 200 hours to produce 10 million softgels. Manufacturing lead time could add another 3 to 10 days to the process. Two-piece capsule equipment Filling two-piece capsules with liquids requires special- ized equipment or modules that equip a powder filler to handle liquids, such as a heat-jacketed hopper that helps the fill material flow better [3]. Cleanliness is another consideration, because it relates to filling accuracy, waste reduction, yields, and production time. In short, the cleaner the operation, the more efficient it is. Cleanliness, however, may entail indexing at low speed to reduce drips between doses, minimize splashes, and pre- vent pressure buildup in the capsules when they're rejoined. Suction can also help with cleanliness, as can a system that detects missing caps or bodies in the segments and prevents the machine from dosing to them. Depending on the capsule filling machine's output, a typical two-shift operation can produce about 600,000 cap- sules per day, including setup and cleaning time. That pre- sumes the machinery assembles and disassembles quickly and has few areas where alignment is critical. Softgel equipment The softgel process differs markedly from two-piece capsule filling. Not only does the machinery fill, it also forms and seals the capsule. That makes the operation more complex and necessitates a variety of special equipment, including a gelatin melter, reactor to prepare the fill mater- ial, encapsulator, tumble dryer, drying trays, and drying tun- nel. The operation may also require a printer or marking system and a system that inspects the size, appearance, and weight of the softgels. As noted above, the need to invest in manufacturing space and machinery leads most companies to outsource softgel production to a contract manufacturing organization (CMO). As with any other project, it's important that you vet the CMOs you're considering. But with softgels, it's 12 January 2016 Tablets & Capsules Depending on the machinery and the formulation, it could take 30 to 200 hours to produce 10 million softgels.