Part 1 discussed the different mechanisms that play a part in the retention of water in a product. As could be seen, the water content of a product can involve some complex dynamics. Determining and controlling the quantity of water held in a product requires an understanding of the dynamics at work. Part 2 looks into the effects that water content has on the products. These are the reasons for wanting to control water activity – in order that the product is maintained in the best condition appropriate for the process that it is in.
aw in the pharmaceutical and chemical industries
The importance of water activity is still not as widely recognised as it should be by the pharmaceutical and chemical industries. Moisture content is very often the only parameter used to define moisture conditions. As illustrated by the following examples, the frequency of water activity measurements should increase, once the significance of this parameter is fully understood.
Water activity, and not %H2O, should be used in the monitoring and control of drying processes. The difference in water-vapour pressure between the drying air and the product is the governing factor. Product vapour pressure is a function of product sorption properties and temperature and moisture content. Drying processes are best controlled by taking these different factors into account.
Simplified moisture checks
Quality control is often concerned with moisture content of products. Very often the problem is more to verify that moisture content is within acceptable limits rather than to accurately measure its value.
Methods for measuring %H2O are often only accurate under laboratory conditions. Special precautions have to be taken when applying them, as results are influenced by variables that are both hard to appreciate and to control.
Provided that quality control requirements are met by a 'Go/No Go' type of measurement, a reliable instrument for measuring aw (or ERH) offers significant advantages. Such an instrument can be more convenient and reliable than a moisture meter. It minimises human error in routine measurements and can be easily calibrated at any time by the operator to certified references.
The method consists of converting the previous %H2O limit into a limit expressed in terms of aw or ERH. Measurements can be statistically analysed to determine the degree of certainty offered by the ERH measurement (including estimation of the practical influence of variables such as product composition and temperature).
Cohesion of tablets, adherence of coatings
Drugs are very often sold in the form of pills and tablets. The powders used for their manufacture are usually dried (eg, fluid-bed dryer) before being pressed to form tablets. The moisture condition after drying is normally submitted to narrow tolerances as it is known that moisture affects the behaviour of powders during and after pressing (cohesion) as well as the adherence of the coatings which may be applied to the tablets.
Specifications on the residual moisture of pharmaceutical powders are often written in terms of moisture content. However, it is the 'free-water' and not the total water content which governs the behaviour of powders. In fact, as some manufacturers have already seen, a water activity check after drying gives excellent results and completely replaces moisture content measurement. The advantages of switching from moisture content measurement to water activity measurement are obvious:
* Measurement of the parameter that really affects the product behaviour.
* Higher resolution and reproducibility of measurements.
* Direct measurement by simple means (less human error).
* Use of instrumentation that can simply be user calibrated, and can be traceable to National Standards.
Specifications written in terms of moisture content can easily be rewritten in terms of water activity by a simple comparison. A further advantage of water activity measurement is that the experience gained from some products can be applied to those under development.
Caking problems during the storage of hygroscopic powders
The absorption of water by a hygroscopic powder causes caking or wetting. During the manufacturing process it is important to determine the humidity value at which this will occur and to maintain satisfactory storage conditions afterwards.
Water-soluble products in powder form, which do not form crystalline hydrates, absorb moisture by forming saturated solutions on exposed surfaces. Excepting absorption in a mono-molecular layer and capillary condensation, absorption of water only occurs when the water-vapour pressure in the atmosphere is greater than the pressure of a saturated solution of the product. Desorption takes place when the latter is greater than the former.
The equilibrium relative humidity (ERH) above a saturated solution of the product is also called critical relative humidity. It corresponds to the %rh value above which the product absorbs moisture from the atmosphere.
In his US patent no. 3 304.767 (Feb 21 1967) Paul R Geissler describes a method for obtaining and measuring saturated solutions of fertilisers with water concentrations similar to those of actual storage conditions. Relative humidity control and appropriate packing materials can therefore be used to eliminate caking problems.
Water activity measurement
Water activity or equilibrium relative humidity is usually defined as the percent relative humidity generated in equilibrium with the product sample in a closed system at constant temperature.
ERH = 100 x aw
Therefore, water activity can be measured with a relative humidity sensor provided that the conditions specified in the above definition are fulfilled.
Practical conditions for measuring aw on product samples
Both the definition of aw and the laws of hygrometry determine practical conditions for measuring aw.
a) Leak proof measurement chamber
The measurement chamber must be tight enough to avoid the influence of outside humidity on measurements. Water molecules are the smallest molecules; therefore the sealing of the measurement chamber should be designed with particular care (a measurement may require several hours).
b) Volume ratio air/product
Moisture content must remain practically constant before and after equilibrium in the measurement chamber. The chamber must be designed in such a way as to ensure that the volume of the air enclosed with the product is kept to a minimum. This volume can be calculated by considering the exchange of water vapour that may take place under the worst possible conditions. The amount of water required by the sensor itself to equilibrate should also be negligible (this is not necessarily the case with hair, plastic or condensation type sensors).
A further factor to be considered is the speed of equilibrium. A small air volume reaches equilibrium with the sample faster than a large air volume.
c) Temperature homogeneity
Any temperature difference between the sensor, the chamber and the sample will result in significant errors. The higher the aw value, the greater the error will be. For example, a temperature difference of 1°C at 0,8 aw and 25°C results in an error of approximately 0,05 aw. A chamber entirely made of metal ensures good temperature homogeneity (this is not true of chambers made of glass).
d) Constant temperature
In practice, constant temperature is necessary to avoid any temperature difference between the probe and the sample. Water activity is usually not very dependent on temperature. However, the ratio of free water to bound water in a product may vary with both the temperature and the total moisture level. For strictly comparable results the temperature of the measurements must always be comparable.
e) Calibrate the sensor and measure preferably at 25°C
Relative humidity instruments are usually calibrated by using diluted solutions (eg, H2SO4) or saturated salt solutions (NaCl, LiCl etc). Other means of calibration are not normally available to most laboratories. The various values published in the technical literature for the ERH of solutions are less contradictory at 25°C than at other temperatures. This temperature is usually recommended for measuring aw.
For measurements involving high accuracy a calibration curve should be drawn according to the recommendations of the FDA (l. Stolff: J. Assoc. Off. Anal. Chem. Col 61 no 5 1978) and the Institute Kulmbach, West Germany (W. Rodel, K. Krispien and L. Leistner: Fleischwirtscharft 59 6), 1979). The values published by the NBS for the ERH of saturated salt solutions between 0 and 100°C may be used when the temperature of 25°C is not convenient (L. Greenspan: Journal of Research of the NBS - A Physics and Chemistry, Vol. 81A no 1 Jan-Feb 1977).
f) Equilibrium time
Significant errors and loss of product stability occur when the process of equilibrium is not observed. The time necessary for reaching equilibrium varies considerably depending on the type of product measured (eg, approx. 5-10 min for a sheet of paper, 10-20 min for cornflour, 1 hr for bakery products, 3-4 hours for meat). It is essential to determine (at least once) the time needed for equilibrium for each kind of product measured. The FDA recommends recording instrument response at 15, 30, 60 and 120 minutes. (With further recording intervals of 60 minutes.) Two consecutive readings, which vary by less than 0,1 aw are evidence of adequate equilibrium.
Dust filters protecting the humidity sensor should be regularly cleaned. Clogged filters significantly increase measuring time and thus create errors.
Many products will generate vapour pressures of volatiles and other contaminants at their surface. It is likely within the confines of the aw measuring instrument that these vapours will contaminate and even destroy the humidity sensor. A method of eliminating this problem is to store an adsorption granular activated charcoal in the sample chamber when not in use. The charcoal will draw off the contaminants, increasing the life of the sensor. Determination of sensor response to calibration standards is by far the best means of confirming instrument response.
Without optimisation of the instrument design to meet product and application specific requirements, it is often impossible to achieve accurate and reliable measurements. Consequently, Rotronic offer a wide range of instruments, which, if correctly selected, will provide many years of service without the need for repeated repair or calibration. Rotronic is represented locally by Action Instruments SA.
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