Humidity – how much is required for tablet making?Print
Poor environmental control, particularly in terms of air humidity can directly affect the pharmaceutical production line in a number of ways. Levels of humidity below 45%RH will allow electrostatic charges to build up in machinery and materials. This can have major implications where flammable solvents are used in the process, so that electrical bonding between machines becomes important. Low humidity can also cause the product to dry out, affecting its performance. Build up of charge on powders can result in poor power flow, and charged products can cause them to stick to each other, leading to packing problems.
High humidity can also cause products to absorb moisture during production and final packaging. Some antibiotic tablets, for example, are degraded and their effectiveness reduced, if moisture is absorbed. Where the product is long-term moisture sensitive it will degrade over time when packed under the wrong conditions. Moisture sensitive formulations are often coated in a thin polymer film to prevent the ingress of water from the atmosphere. But the coating of polymer films itself requires careful environmental control to ensure that a smooth uniform finish can be achieved and that the outer surface of the tablet can be printed with water-soluble ink.
The issue of humidity is therefore an important one for the tablet manufacturer, but also complex, since there may well be different requirements for the moisture content of atmospheres at different steps in the manufacturing process. Therefore, the control of the production environment is becoming more critical as product development moves forward.
Conventional humidification control
Air conditioning and handling equipment based on refrigeration cycles – heating ventilation and air conditioning (HVAC) systems, is generally built to condition working environments so as to maintain levels of relative humidity between 40 and 60%, with temperatures around 21 – 25°C. It is felt that the environment needs to be controlled for personal comfort, and it is assumed that the product will also be stable in this wide-ranging environment. It is not until low productivity levels are found, and production problems are traced back to the temperature and humidity control, that the importance of the right equipment can be truly seen. It is important to control the humidity and temperature of the atmosphere in all of the tablet production areas. Indeed environmental control within an individual production machine such as a rotary tablet press can also have critical bearing on the quality of the final product.
Wet granulation processes can be carried out in humid environments since the formulations contain water. By contrast, dry granulation, which is often necessary for moisture sensitive APIs such as antibiotics, requires the relative humidity of the surroundings to be as low as possible to give the materials the best chance of surviving the production process. Generally speaking tablet compression machines require the products to be dry and low humidity of the surrounding air is beneficial, especially if the drug or formulation excipients are sensitive to moisture. However, there is also a danger in making the air too dry in that electrostatic charges may build up in the powders, causing flow problems and materials to clog flow lines. Poor filling of dies can then lead to defective tablets. The required level of humidity for the compression process is therefore largely governed by the degree of hydrophilicity of the components in the formulation. There is no single answer to the required level of humidity for tablet making.
When tablets are coated with aqueous based polymer films or with sugar coats, extremely tight control of air humidity is required to ensure that the coating does not dry too fast or too slowly. There are also pharmaceutical printing processes that require control of humidity between 95 and 98%RH, with temperature control to better than 1ºC, to prevent water based inks from drying during processing.
What technologies can give the required humidity?
Relative humidity levels below 40% can be achieved with a rotary dessicant dryer. These machines have been in use for many years and can be sized according to the work area that needs to be dried. They function by passing a stream of ambient air through a solid dessicant (typically silica gel) located within a rotating wheel or bed. The exit air from the rotary dryer may have a relative humidity of 1% or lower, and it may be necessary to blend this air stream with another to achieve the required level of humidity for the particular manufacturing equipment or process. Flow control is therefore important. Water that is absorbed from the air by the dessicant is released by the dessicant bed rotating into a stream of hot air. The resulting wet air is usually vented outside the building.
If the relative humidity of the environment is too low, for example in the case of the area where tablets are printed with water-soluble inks, it may be necessary to increase the humidity of the atmosphere. There are several commercial humidifiers that can be used for this purpose. Electrode boiler steam humidifiers are expensive to run but are good means of ensuring high humidity. Savings can be made if process steam is available in the facility as this can be used to indirectly heat pure water, thereby saving in the cost of electricity needed for raising steam. More savings still can be made by using a cold water humidifier as the water does not need to be heated.
Cold water humidifiers have had a bad press in the past because of fear about the safety in respect of Legionella or other bacterial spores. The UK Health and Safety ACOP L8 document states that, provided the systems meet all the requirements of the L8 code of practice, there is no more significant risk than using steam systems - in some cases less. It is also often assumed that, because a system is steam based, there is no risk. Unfortunately, this may not always be the case.
The major advantage of cold-water humidifiers is that they use less than 10% of the energy required by steam humidifiers. Also, because the principle of cold-water humidification is adiabatic, free cooling of the atmosphere can be achieved. This can result in cost savings, not only in winter, the main humidification season, when the return air from the production area is warm and typically large quantities of fresh air are used to give free cooling, but also in the summer, when the outside ambient temperatures are high, the air can be cooled by up to 6ºC by the humidifier.
Control and maintenance
In deciding what level of humidification is required and the technology required to achieve this, attention has to be given to the method of control. In pharmaceutical R&D, the control of humidity and temperature can have major implications in bringing a product to market. This may be from a production point of view, where the yields are often low until the humidity and temperature are accurately controlled; pharmaceutical coating applications are a prime example of this, as is stability testing of pharmaceutical products.
In both of these areas, the control of the environment has been found to be critical. Poor control can give variations in coating, making it necessary to reject entire production batches, often amounting to thousands of pounds worth of stock. More importantly, falling outside of control parameters in long-term stability testing will lead to a restart. This can put weeks, or even months, on to the research and development time of a new product, enabling competitors to launch similar items sooner and gain that all important competitive advantage.
In addition to control, the maintenance of equipment must be factored into the cost of humidification or dehumidification. Installation of such equipment requires a full understanding of, not only the application, but also the design and control of the process. Selection of the right equipment for the particular application and the support of the equipment once installed are critical to the long-term reliability and operation of the system. When considering the how the right level of humidification is to be achieved for tablet making, it would be most beneficial to consult a specialist environmental control expert instead of a regular HVAC engineers.