Dilution should, in theory, allow the operator to be exposed to larger amounts of the processed material without any adverse pharmacological effect. However, powders tend to segregate based on particle size and density. Most process equipment is designed to minimize this behavior but any product that is outside the process equipment could segregate if the material shows these characteristics. Segregation causes the mixed product to separate by raw material type, therefore pockets of concentrated API could be found. This behavior is highly product dependent but has been seen in many processes and should be considered in the design and selection of equipment and facilities. In general, product entering the tablet press room has gone through a granulation process via wet granulation, oscillators, roller compactors, etc. followed by a milling step. Granulated powder typically has the active ingredient better distributed through the granules formed on this step. Segregation may not be much of a problem since particle size and density of the granules has been controlled. Processes that do not incorporate granulation steps prior to compression have to be analyzed for potential exposure due to API segregation. In order to put levels of containment into perspective, one sugar crystal weighs approximately 3 milligrams. One microgram is 3,000 times less than that single crystal.
When designing a contained tablet press room, the designer must establish how this facility will be used based on containment category. Considerations regarding the facility being single or multi-product will impact the design of the facility which affects room layout and pressurization. In contained facilities, pressurization of the room should be negative with respect to the surrounding environment provided that the air entering the facility meets the room classification. However, in a multi-product facility, this might create cross contamination so a different scheme is required- typically still negative pressure relative to the connecting room but usually an airlock is provided. The airlock would be positively pressurized relative to the process room and also to the common corridor. In some cases, for even lower chance of migration, a cascaded airlock configuration would be designed. Further, gowning, de-gowning, mist showers and material airlocks within each compression room will be required to avoid cross contamination. The drawing below depicts a layout and room pressurization design for a high containment multi-product facility. It is important to note that HVAC pressurization for containment facilities varies depending on the type of facility, adjacencies, production and containment requirements
Sampling: Consideration must be given to what type of sampling and testing (i.e. hardness, weight, friability) will take place and the location where it must be performed. A sampling isolator may be required based on the sampling protocols. The operator must be able to obtain the sample from the tablet press in a contained manner and dock the sample to the sampling isolator. Some tablet presses have automated sampling devices which must also be isolated. Note that design of the contained disposal of the tablet remnants is required as well. Tablet receiver: There are several types of tablet receiver technologies. Some include the use of a continuous liner which is double-tied and clipped once the liner is filled. Some manufactures use 200L-500L bulk bags with double tie and clip connections to reduce the amount of handling. Most common are stainless steel tablet bins or stainless steel drums with containment valves. Due to the amount of changeover time that any of these options have, some vendors have incorporated a double valve system where one drum is being fed with tablets while the other is being disconnected from the system. The bins and stainless steel drums must be cleaned in the contained manufacturing area wash room.