Virtually all materials interact with water. Accurate determination of a product’s water content and mechanism of water–solid interactions is required to define suitable processing, packaging, storage conditions, shelf life and use. Techniques used to achieve this—gravimetric moisture analysis, Karl Fischer titration and differential scanning calorimetry (DSC)—and methods for studying water–solid interactions—sorption testing and water-content-dependent mechanical analysis—are discussed in this article.
Moisture content, which is the sum of all volatile liquids included in a solid, influences the physical properties of a substance, including weight, density, viscosity, refractive index, electrical conductivity and glass transition temperature. Loss-on-drying (LOD), chemical and thermogravimetric techniques are commonly used to determine the content. Humidity is a term that is selective for the water content.
Moisture content determination in solids
A dedicated moisture analyzer such as that shown in Figure 1 is frequently used in industry for quality control, production, inspection and receipt of solid or semisolid materials. All moisture analyzers apply the LOD method.
The drying process is done with infrared energy using a halogen bulb or a metal tubular heating element. This measurement reveals whether a product intended for trade or production has the following properties:
- Agglomeration, in the case of powders
- Microbiological stability
- Powder-flow properties, viscosity
- Dry-substance content
- Concentration or purity
- Commercial grade (in compliance with quality agreements)
- Nutritional value
- Legal conformity (food regulations).
Water content determination in nonaqueous liquids
Karl Fischer titration (Figure 2)1 is used to determine water content based on the following chemical reaction2:
H2O + I2 + SO2 + CH3OH + 3 RN -> [RNH] SO4CH3 + 2 [RNH]I
Figure 2 – Schematic of Karl Fischer techniques. Left: volumetric titration— iodine is added by a burette during titration. Right: coulometric titration— iodine is generated electrochemically during titration.
The endpoint is detected as a trace of excess iodine (I2). Two methods can be used for this determination: volumetric and coulometric titration. Coulometry is much more sensitive, with detection limits in the ppm range. Moisture determination with Karl Fischer titration is specific for water; the method is also suitable for soluble solids or water if it can be removed by heating in a stream of gas or by extraction.3
Moisture determination with thermal analysis
Thermal analysis (TA) enables the determination of trace samples as well as sources of moisture in small samples. TA techniques are described below.
Differential scanning calorimetry
On a DSC curve, water release appears as an endothermic peak that is typically very broad (see Figure 3). If water release is overlapped by other effects, it can be separated by applying higher pressure in a high-pressure DSC or by using temperature-modulated DSC, where water release is visible only on the nonreversing curve.4
Figure 3 – Water-content determination in water-saturated polyamide 66 with TGA (top) and DSC (bottom). The TGA step evaluation quantified 3.6%; the DSC content evaluation of the broad endothermic peak revealed 3.98%, which are in agreement.
Thermogravimetric analysis (TGA) provides comprehensive information on mass change, characteristic temperature ranges for moisture release and information on kinetics. Moisture and water are often determined with TGA. Release of water appears as a weight-loss step at a certain temperature that is easily evaluated and ideally quantifies the amount of water present in a sample (Figure 3). Varying the heating rate for TGA provides the data for kinetic evaluations. The technique allows kinetic parameters to be calculated and predictions about long-term behavior of the samples to be made.
Care must be taken with the applied temperature. The sample may decompose before the water is expelled completely. Special standard methods have been established for this purpose. A vacuum is applied in order to shift the water release to lower temperatures.5
Evolved gas analysis
Adsorbed water, water of crystallization and other solvents can be distinguished if thermal analysis, most often TGA, is combined with a gas analyzer such as a mass spectrometer (MS) or Fourier transform infrared (FTIR) spectrometer. The gas analyzer identifies the type of molecule released at a certain temperature.6
Dynamic mechanical analysis
The mechanical properties of materials are also dependent on moisture content. A water-saturated polyamide has a much lower glass-transition temperature than the same dry one. Here, water acts as a plasticizer.
Biological materials such as hydrogels are normally analyzed in a humid environment because they demonstrate different properties in a dry state. Accessories for dynamic mechanical analysis (DMA) have been developed for these measurements, such as a humidity chamber that allows DMA measurements under controlled humidity. Another option is to submerse samples in a temperature-controlled bath.7
Figure 4 – SPS multi-sample dynamic vapor sorption test system (METTLER TOLEDO). Up to 23 samples can be analyzed simultaneously.
Dynamic vapor sorption
Water interactions with solids can be determined using dynamic vapor sorption (DVS), a gravimetric technique that measures variations in sample weight while subjecting the sample to changing relative humidity. Meaningful results can be obtained if several samples are measured simultaneously under the same conditions of humidity and temperature. This is only possible with multi-sample test systems that provide high sample throughput, optimized (meaning shorter testing time measurements conducted in series) and comparability of different batches or types of samples (see Figure 4).8 The curves acquired with a DVS system allow the following determinations.
Sorption isotherms can be calculated and compared to those included in the Brunauer, Deming, Deming and Teller (BDDT) classification. The isotherm provides information on the mechanism of sorption that is dependent on the strength of the interaction between the solid surface and vapor molecules.9 Dynamic gravimetric Brunauer-Emmett-Teller (BET) surface area determination can be done in the case of a monolayer distribution of vapor molecules. This can be carried out at ambient temperatures and pressure as opposed to classical BET with nitrogen or argon, which requires low temperatures and vacuum.
The effect of sample mass and particle size on sample diffusion rate can be investigated.
Amorphous content determination
There are often dramatic differences in the moisture-uptake capacity of a substance’s crystalline and amorphous states. Due to increased free energy, void space and surface area, the glassy state takes up more water. During a measurement with increasing relative humidity, the material may change from an amorphous to a crystalline state. This results in significantly reduced water-uptake capability and leads to mass loss because excess water is desorbed during crystallization. The mass loss can be used to track the transition from amorphous to crystalline state. For quantification of amorphous content, DVS can be applied to determine amorphous content of less than 1%.
Diffusion and permeation
A sorption test system can be used for permeation measurements on film material. For this, the film is clamped between a ring and a sample container. A small quantity of drying agent is placed into the container for diffusion measurements; for out-diffusion measurements (diffusion out of the closed compartment consisting of the sample container and membrane, which acts as a lid) a droplet of water is placed inside the container.10
A multi-sample DVS can accommodate special sample trays to contain small packaged materials like tablets and larger objects like printed circuit boards. Samples can thus be measured directly in the test chamber.11
Additional simultaneous measurements
With a multi-sample DVS, the sample can be viewed from above using a camera with illumination, or Raman measurements in timed increments can be made. Measurements typically last from days to weeks. Automatic recording of images and measurement of additional data deliver complementary information that facilitate interpretation of sorption curves (see Figure 5).
Figure 5 – Simultaneous measured dynamic sorption curves of 11 different samples;
x-axis experiment duration 30 days,
y-axis change of weight in %, isothermal at 25 °C, blue dotted line relative humidity in %.
Many options are available to determine water content and investigate water–solid interactions. The technique selected depends on the type of sample and property of interest, and may include a moisture analyzer, Karl Fischer titration, thermal analysis and instrumentation for dynamic vapor sorption.
- Fischer, K. Neues Verfahren zur massanalytischen Bestimmung des Wassergehaltes von Flüssigkeiten und festen Körpern. (New process for the titrimetric determination of water content of liquids and solids) Angew. Chem. 1935, 48, 394–6.
- Wünsch, G. and Seubert, A. Stöchiometrie und Kinetik der Karl-Fischer- Reaktion in Methanol als Reaktionsmedium (Stoichiometry and kinetics of the Karl Fischer reaction in methanol as the reaction medium). Fres. Z. Anal. Chem. 1989, 334, 16–21.
- Muhr, H.J. and Rohner R. METTLER TOLEDO: Good Titration Practice in Karl Fischer Titration, 2011, 51725145B, 86 pages.
- Schawe, J.E.K. and Hess, U. influence of moisture on the glass transition of a spray-dried compound using the Isostep™ method. J. Thermal Anal. Calorim. May 2002, 68(2), 741–9.
- United States Pharmacopeia 39, Monograph Imipenem, Loss on drying; Chap <891>.
- Darribère C. Evolved gas analysis; METTLER TOLEDO: Thermal Analysis Application Handbook, 2010, 51725056A, 68 pages.
- Reutzel-Edens, S.M. and Newman, A.W. Physical characterization of hygroscopicity in pharmaceutical solids; Chap 9, pp 235–42. In Hilfiker, R., Ed. Polymorphism in the Pharmaceutical Industry; Wiley-VCH: Verlag GmbH & Co. KGaA, 2006.
- proumid.com/wp-content/uploads/2015/11/AN_1201_Water_Vapor_ Permeability_Films.pdf
- proumid.com/wp-content/uploads/2015/12/AN_1501_Vapor_ Sorption_Product_Packages.pdf
Matthias Wagner, Ph.D., is product manager at METTLER TOLEDO GmbH, Analytical, business unit MatChar, Sonnenbergstrasse 74, Schwerzenbach, CH-8603, Switzerland; tel.: +41 44 806 7477; e-mail: [email protected]; www.mt.com/ta