Moisture isotherm

Moisture isotherms were, up until recently, not considered part of preformulation. However, with the advent of microcalorimetry, moisture isotherms and surface areas may be determined with mg quantities of drug substance [29,30]. 

Idealized moisture isotherms are presented in this article for substances that sorb moisture in discrete stages (e.g., crystalline materials capable of forming a hydrates) and for substances that do not interact with water in discrete stages. These idealized isotherms form a basis for the discussion of deviations and unexpected effects of moisture sorption that can influence the physical or chemical properties of the solid. 

Figure 4. Moisture isotherm at 23°C for the paper used in this degradation study...

For any type of product that gains or loses water, one can measure the moisture content as a function of relative humidity, or water activity, and determine a moisture isotherm. As shown in Fig. 14.14, moisture isotherms are usually sigmoid shaped curves. However, one can sometimes use only the linear portion of the curve for shelf life predictions. 

Now suppose that a product is stored in a real world situation where the moisture on the inside or the outside of the package changes over time. Then one needs the external environmental conditions and a moisture isotherm for the product. The moisture on the inside of the package may change over time even if the external conditions are constant because the product is reaching equilibrium with the internal moisture content. If the external conditions vary over too wide a range of temperatures, then multiple isotherms may be needed. 

FIGURE 1.6 Typical equilibrium moisture isotherms at room temperature for selected substances (1) asbestos fiber, (2) PVC (50°C), (3) wood charcoal, (4) Kraft paper, (5) jute, (6) wheat, (7) potatoes. 

Moisture isotherms pertain to a particular temperature. However, the variation in equilibrium moisture content for small changes of temperature (<10°C) is neglected [3]. To a first approximation, the temperature coefficient of the equilibrium moisture content is proportional to the moisture content at a given relative humidity ... 

However, diffusion coefficients based on concentration gradients are still commonly employed as a means of describing the rates of moisture movement. In general, the diffusion coefficient will be a function of both concentration and temperature. At constant temperature, the diffusion coefficient is only independent of concentration if the moisture isotherm is linear or the moisture unbound. Isotherms for many fibers are approximately linear over the range of relative humidity from 20% to 80%, as the data in Eigure 37.1. Thus, in a number of practical applications, the assumption of a concentration-independent diffusivity can lead to useful results. 

It is ideal to develop equilibrium moisture isotherms for granulations to understand the moisture content at different humidities. To develop moisture isotherms granulations are exposed to different relative humidities at a set temperature and the equilibrium moisture content is determined. This information could be used to develop specifications for the moisture content of the granulation and would help device ideal processing and packaging conditions. One application of moisture... 

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