An exclusive Q&A with Pharma Technology Inc. about capsule manufacturing best practices, dedusting and polishing, and what’s on the horizon for this method of delivery in 2017.
Each year, capsules become increasingly more sophisticated. With various types of capsules available—such as hard and soft gelatin capsules, enteric coated capsules, sustained release capsules, and rectal capsules—pharmaceutical manufacturers must not only select which type of capsule ensures the most advantageous delivery of their drug product, but they must also navigate (and be attentive to) the operational best practices for this method of delivery.
Nic Michel, General Manager, North America, for Pharma Technology Inc.—a company that designs and manufactures specialty dedusters, metal detecting devices, and loading systems for tablet- and capsule-producing machinery—participated in an exclusive Q&A with Pharmaceutical Processing. His edited responses are below.
To start, in what instances would a capsule be preferable to another method of delivery?
A capsule is the method of choice for materials that cannot be compressed into a tablet due to intrinsic properties (poorly compressible powders, certain granules or pellets, mini-tabs, etc.).
What are some of the advantages to delivery of a medication via a capsule?
- Standardized size and shape.
- Formulation is easier than with a tablet, where the relationship between tablet hardness and dissolution needs to be balanced.
- Allows combination of multiple dosage forms into one capsules (e.g. pellets plus minitab plus powder).
What are some of the disadvantages to delivery of a medication via a capsule?
- Capsule filler typically at maximum speeds of 3,000 per minute with 00 size capsules when tablet presses can easily reach double the output with same size caplet.
- Costs of empty capsules.
- Lesser yields on a capsule filler when compared with a modern tablet press.
- All these factors combine to make the cost of producing capsules higher than the cost of tablets for a same product.
Are there certain drugs (or APIs) that aren’t well-suited to delivery through a capsule?
An API must be able to flow through dosing disc with a tamping style capsule filler or, with a dosator style capsule filler, be vacuumed via pipette. Otherwise, the API may need to be granulated or layered onto pellets.
In terms of manufacturing, what have you found to be some of the greatest challenges with capsules? How do these challenges arise? What are some of the best ways to address them?
- Markings on printed capsules tend to be shed during the polishing process when using traditional brush/tube polishers mounted at a 30° angle. Residual powder seems to stay inside the lower part of the polisher tube and be picked up by the brush when it rotates. This constant ingress of powder on the brush sands off the relatively delicate ink markings on capsules.
- When filling powder into capsules, there seems to always be powder around the rim where the two parts of the capsules join. Again, traditional polishers mounted at a 30° angle tend to have residual powder in the lower part of the tube which, when picked up by the rotary brush, results in ingress around the capsule joint.
- Vertical capsule polishers do not allow residual powder to accumulate between the rotary brush and the tube. Residual powder either falls to the bottom of the polisher and is vacuumed away, or is flicked from the rotary brush by a fixed lateral brush and vacuumed from the side through a dust extraction shroud, which ensures that the main rotary brush remains clean for longer.
What have you found to be the best practices for capsule development/production/manufacturing?
- Always use a vertical polisher, metal detector, and empty capsule eliminator directly after the capsule filler
- Make sure the capsule picked can withstand polishing process and handling through a metal detector and container.
Would you say some of these capsule best practices are often overlooked?
Capsule polishing is often an afterthought. Most development labs work on such small scale that they do not own a full size polisher and will dedust capsules over a screen and polish them with a hand brush. So it is difficult to replicate a true polishing process running at 3,000 caps per minute with capsules coated in residual powder.
Have you found that companies tend to excel in a specific part (or parts) of the capsule development/production/manufacturing process?
The main target of capsule development is getting a process that gives accurate dosage and dissolution for obvious regulatory reasons. Production and manufacturing must then make the process run in an economically viable manner with yields and uptime on target.
Why is dedusting and polishing an important step in the capsule production process?
If capsules are not dedusted and polished, a lot of residual dust may make its way into the packaging equipment, resulting in obscured sensors, powder ingress in mechanical gears, belts, etc. This then leads to downtime and higher maintenance costs in packaging, bottles or blisters not sealing product properly, and patient compliance issues if the capsules do not appear cosmetically clean.
What are some of the necessary steps for the packaging and transportation of capsules?
- Polishing ensures capsules are clean and do not transfer residual powder onto packaging equipment.
- Metal checking capsules directly after the polisher makes sure any capsule contaminated with metal is removed from the flow of production as early as possible. At this stage, it is possible to separate individual capsules. If metal detection takes place after packaging, then complete blisters, bottles, or cartons have to be pulled out of the production flow.
- Empty capsule elimination also best takes places prior to packaging to avoid transferring empty capsules into bottles or blisters which then have to pulled off line and reprocessed.
What are the primary texture concerns for capsules? How can these concerns best be addressed?
Capsules have to be able to withstand the mechanical process of polishing and then the handling through a metal detector, empty capsule sorter, and transfer onto packaging equipment. When using printed capsules, it is essential they are thoroughly tested to ensure the ink marking can withstand these steps.
In your opinion, what has been one of the greatest leaps/improvements in capsule manufacturing in recent years?
Capsules seem to be enjoying a renewal in the pharmaceutical industry, especially with modified release versions of drugs previously available in immediate release form, usually for the purpose of patent extension (or circumvention). The capsule format allows for multiple dosage forms to be combined into one (e.g. power for IR, pellet for MR filled inside one capsule).
What are some of the trends you’re seeing in capsule manufacturing? Anything new on the horizon for 2017?
We are seeing a trend toward more compact, more integrated solutions in the production room. Some of our customers demand a system that will polish, metal check, eliminate empty capsules, sample groups of capsules off line, test capsules against a predefined recipe, and then provide feedback to the capsule filler regarding weight or closing—all in a compact footprint that fits in limited production space.