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Moisture sorption characteristics of excipients
 
Q: What role does moisture content play in API stability?
 
 
imageThe moisture content of excipients plays an important role in the physical and chemical properties of pharmaceutical products. The characteristics of the excipients for a particular dosage of a formulation depend on their moisture sorption behavior, flowability, and stability during manufacturing and storage. Defined as any substance other than the API that has been appropriately evaluated for safety, a drug delivery system includes them for the following reasons [1]:
  • To aid processing of the system during its manufacture,
  • To protect and support stability, bioavailability, and patient acceptability,
  • To assist in product identification,
  • To enhance any other attribute that promotes the overall safety and effectiveness of the API during storage or use.
 
Manufacturers classify excipients according to their functions as sweeteners, preservatives, binders, lubricants, flow enhancers, film formers, fillers, disintegrants, diluents, and so on.
 
According to a study by Dave in 2008, the most common excipients are lactose; microcrystalline cellulose (MCC), a diluent; sodium starch glycolate; croscarmellose sodium, a disintegrant; colloidal silicon-dioxide, a glidant; hydroxypropyl methylcellulose (HPMC); polyvidone (PVP); lactose hydrous; starch, a binder; magnesium stearate, a lubricant; and titanium dioxide, an opacifier [2].
 
The presence of water in the excipients is very critical in terms of stability, flow, dissolution, compaction, and storage. The hygroscopicity of an excipient is its ability to interact with moisture from the surrounding atmosphere, and the mechanisms of moisture sorption for various excipients are different. Therefore, you need to understand the moisture-sorption characteristics of any excipient before working on any formulation of APIs.
 
Pharmaceutical scientists call the equilibrium relative humidity (ERH) of the excipient, i.e., the vapor pressure inside and outside the material, water activity (aw). It is a measure of the free moisture in the material. The aw influences a combination of water-solute and water-surface interactions and capillary forces.
 
Two types of sorption, adsorption and desorption, occur. Adsorption refers to moisture that adheres to the material, whereas desorption refers to the removal of moisture from the material. The adsorption and desorption characteristics depend upon the temperature, relative humidity (RH), and composition of the material.
 
Generally, the aw increases as the temperature increases. The moisture content of an excipient at ERH is called equilibrium moisture content (EMC). At EMC, the material adsorbs or desorbs no moisture at a particular temperature and RH. The microbial stability, chemical stability, flow properties, hardness, compaction, and dissolution rate depend on the aw of excipients.
 
imageFigures 1 and 2 show the differences in vapor pressure that 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 surrounding environment with a lower vapor pressure.
 
imageTwo types of moisture adsorption occur, physical and chemical. Physical adsorption, or physisorption, uses van der Waals interactions and is reversible. In chemical adsorption, or chemisorption, material adsorbs molecules by chemical bonding, and the process is irreversible [3]. Different forms of adsorption and desorption exist. The most common form is the sigmoidal shape shown in Figure 3. The difference between adsorption and desorption is called hysteresis.
 
The RH of the surrounding environment at a particular temperature, from which an excipient could absorb moisture from the atmosphere, 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. Those figures show that sodium bicarbonate powder is stable below 76 percent RH at 25°C and below 48 percent RH at 40°C [4]. The exposure of an excipient to RH above the critical RH creates a liquid state that accelerates chemical and physical changes.
 
Using the Guggenheim, Anderson, and de Boer (GAB) model, pharmaceutical scientists commonly use the GAB equation to model the moisture sorption characteristics of excipients, where MC is the moisture content of the excipient (dry basis, decimal); wmis the moisture content adsorbed or desorbed, corresponding to the monomolecular layer; aw is the water activity; and K and C are constant parameters.
 
jrs
 
The sorption parameters for the excipients MCC, carboxymethyl cellulose (CMC), HPMC, and polyvinylpyrrolidone (PVP) are found in Crouter and Briens' article "The effects of moisture on the flowability of pharmaceutical excipients" [5]. Based on the moisture-sorption characteristics, you can identify the range of moisture content for an excipient that falls under the CRH at a particular environmental condition. As the temperature of the environment changes, those characteristics change, and a material's behavior changes. The best practice is to identify the right environment, understand the material's behavior, and modify the conditions of the work environment to suit the material's processing.
 
References
  1. Airaksinen S, Karjalainen M, Shevchenko A, Westermarck S, Leppänen E, Rantanen J, Yliruusi J. Role of water in the physical stability of solid formulations. J Pharm Sci. 2005, 94: 2147-2165.
  2. Dave RH. Overview of pharmaceutical excipients used in tablets and capsules. Drugs Topics, October 24, 2008.
  3. Rouquerol F, Rouquerol J, Sing K. In: Adsorption by powders and porous solids. Academic Press: London, UK, 1999.
  4. Kuu W, Chilamkurti R, Chen C. Effect of relative humidity and temperature on moisture sorption and stability of sodium bicarbonate. Int J Pharm, 1998, 166:167-175.
  5. Crouter A and Briens L. The effects of moisture on the flowability of pharmaceutical excipients. AAPS PharmSciTech, 2014, 15(1): 65-74.

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