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Tablets & Capsules September 2018 45 sition of a material, either adsorption or desorption will occur. Adsorption refers to moisture adhering to the material; desorption refers to the removal of moisture from the mate- rial. The moisture content of an excipient at ERH is called the equi- librium moisture content (EMC). At EMC, the material adsorbs or desorbs no moisture at a particular temperature and RH. The microbial stability, chemical stability, flo w properties, hardness, compaction, and dissolution rate of a formulation depend on the a w of its excipients. Figures 1a and 1b show how dif- ferences in vapor pressure influence the mechanisms of adsorption and desorption. Moisture adsorbs from a surrounding environment with a higher vapor pressure into material with a lower vapor pressure, whereas moisture desorbs from material with a higher vapor pressure into a sur- rounding environment with a lower vapor pressure. Two types of moisture adsorption occur, physical and chemical. Physical adsorption, or physisorption, uses van der Waals interactions and is revers- ible. In chemical adsorption, or chemisorption, material adsorbs mole- cules by chemical bonding, and the process is irreversible [3]. Different forms of adsorption and desorption exist. The most common form can be represented by a sigmoidal curve with the x-axis representing the a w and the y-axis representing the moisture con- tent in the material, as shown in Figure 2. The difference between the adsorption and desorption curves in the figure is called hysteresis. The RH of the surrounding envi- ronment at a particular temperature, from which an excipient could adsorb moisture from the atmo- sphere, limits the critical relative humidity (CRH) of the excipient. For example, the CRH of the excipient sodium bicarbonate powder lies between 76 percent and 88 percent RH at 25°C and between 48 percent and 75 percent RH at 40°C. This means that sodium bicarbonate pow- der is stable below 76 percent RH at 25°C and below 48 percent RH at 40°C [4]. Exposing an excipient to RH above the critical RH creates a liquid state that accelerates chemical and physical changes. Pharmaceutical scientists com- monly model the moisture sorption characteristics of excipients using the Guggenheim, Anderson, and de Boer (GAB) equation, as follows: M C = w m CKa w (1 − Ka w ) × (1 − Ka w + KCa w ) where MC is the moisture content of the excipient (dry basis, decimal); w m is the moisture content adsorbed or desorbed, corresponding to the monomolecular layer; a w is the water activity; and K and C are constant parameters. The sorption parameters for the excipients MCC, carboxymethyl cel- lulose (CMC), HPMC, and polyvin- ylpyrrolidone (PVP) are found in Crouter and Briens' article "The effects of moisture on the flowability of pharmaceutical excipients" [5]. Based on the moisture-sorption char- acteristics, you can identify the range of moisture content for an excipient that falls under the CRH at a particu- lar environmental condition. As the temperature of the environment c h a n g e s , t h o s e c h a r a c t e r i s t i c s change, as does the material's behav- ior. The best practice is to identify the right environment, understand the material's behavior, and modify the conditions of the work environ- ment to suit the material's require- ments for processing. T&C References 1. S. Airaksinen, M. Karjalainen, A. Shevchenko, S. Westermarck, E. Leppänen, J. Rantanen, and J. Yliruusi, "Role of water in the physi- cal stability of solid formulations," Journal of Pharmaceutical Sciences, 2005, Vol. 94, pages 2,147-2,165. 2. R.H. Dave, "Overview of phar- maceutical excipients used in tablets and capsules," Drugs Topics, October 24, 2008. 3. F. Rouquerol, J. Rouquerol, and K. Sing, In: Adsorption by powders and porous solids, Academic Press, London, UK, 1999. 4. W. Kuu, R. Chilamkurti, and C. Chen, "Effect of relative humidity and temperature on moisture sorp- tion and stability of sodium bicar- b o n a t e , " I n t e r n a t i o n a l J o u r n a l o f Pharmaceutics, 1998, Vol. 166, pages 167-175. 5. A. Crouter and L. Briens, "The effects of moisture on the flowability of pharmaceutical excipients," AAPS PharmSciTech, 2014, Vol. 15, No. 1, pages 65-74. John Lawrenceis research director at the Bulk Solids Innovation Center, Kansas State University (https://bulk- solids.k-state.edu/index.html). Figure 2 Sigmoidal adsorption and desorption curves Moisture content Water activity (a w ) Desorption Adsorption