Hydrates moisture sorption

Determine the solvation/desolvation behaviour depending on the vapour pressure of the solvent (hydrates moisture sorption/desorption isotherm). 

Fakes et al. [1.152] evaluated the moisture sorption behavior of mannitol, anhydrous lactose, sucrose, D-(+)-trehalose, dextran 40 and povidine (PVP K24) as bulking agents. Mannitol was found to be crystalline and non-hygroscopic before and after freeze-drying with RM 0.1-0.3% w/w at 25 °C and 10-60% RH. Anhydrous lactose, sucrose and trehalose were crystalline and relatively non-hygroscopic with RM 0.86, 0.15 and 9.2% respectively. After freeze-drying they where amorphous with RM 1.6, 2.5 and 1.2%, respectively, and adsorbed moisture in an increasing RH atmosphere. Lactose adsorbed 10% water and formed its crystalline hydrate at 55% RH. 

In essence, the test battery should include XRPD to characterize crystallinity of excipients, moisture analysis to confirm crystallinity and hydration state of excipients, bulk density to ensure reproducibility in the blending process, and particle size distribution to ensure consistent mixing and compaction of powder blends. Often three-point PSD limits are needed for excipients. Also, morphic forms of excipients should be clearly specified and controlled as changes may impact powder flow and compactibility of blends. XRPD, DSC, SEM, and FTIR spectroscopy techniques may often be applied to characterize and control polymorphic and hydrate composition critical to the function of the excipients. Additionally, moisture sorption studies, Raman mapping, surface area analysis, particle size analysis, and KF analysis may show whether excipients possess the desired polymorphic state and whether significant amounts of amorphous components are present. Together, these studies will ensure lotto-lot consistency in the physical properties that assure flow, compaction, minimal segregation, and compunction ability of excipients used in low-dose formulations. 

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. 

Hailwood-Horrobin Solution Sorption Theory. The Hailwood-Horrobin (57) model treats moisture sorption as hydration of the polymer, taken here to be dry wood, by some of the sorbed water called water of hydration, m. The hydrate forms a partial solution with the remaining sorbed water, called water of solution, m,. An equilibrium is assumed to exist between the dry wood and water and the hydrated wood with an equilibrium constant K. Equilibrium is also assumed to exist between the hydrated wood and water vapor at relative vapor pressure h, with equilibrium constant K2. A third constant is defined as the moisture content corresponding to com-... 

Dynamic moisture sorption, in particular, provides an excellent opportunity to study solid form conversion Fig. 18.6 depicts a typical sorption curve of an antiarrhythmic compound that shows the conversion of an anhy-drate to a monohydrate. Moisture uptake by the anhydrous form is very small on the moisture uptake curve until a critical humidity of about 70% is achieved. At this point, rapid moisture uptake occurs and a hydrate form containing 10%moisture is generated. Subsequent reduction in the humidity (desorption) shows the hydrate to remain until approximately 5% RH, when it spontaneously converts to the anhydrous form. It is important to recognize, however, that conversion between solid forms is very time dependent. The relative humidities at which conversion was seen in Fig. 18.6 are significantly dependent on the length of time the solid material was equilibrated. For the material shown in Fig. 18.6, conversion from the anhydrous to the hydrate "at equilibrium" will occur somewhere between 10 and 70% RH. More precise determination of the critical humidity at which conversion occurs may be determined as described in Section 2.3.1. 

From a thermodynamic point of view, one might expect that polysaccharide crystallites would display distinct hydrates and not show continuous variation in water content as a function of relative humidity. So far, the continuous variation in unit-cell parameters as a function of relative humidity seems to be the rule. However, the variation of cell parameters with relative humidity seems to follow the shape of the moisture sorption curve.(] ) In all probability, the fine structure factor introduces localized strain effects which prevents detection of a unique hydrate at a given relative humidity. 

The most obvious effect of changes in a solid API s water activity can be formation or loss of waters of hydration from the API crystal lattice. In some cases, loss of waters of hydration ean lead to the complete conversion of the API to an amorphous form, which in turn can lead to greater chemical instability. Eortunately, such effects are generally well-known with a given API based on moisture sorption isotherms (i.e., water uptake and loss measured using sensitive balances as a function of relative humidity). 

It should be stressed, that a successful analysis of solvated crystal forms requires additional methods besides those mentioned with true polymorphs. Such methods are, for example, thermogravimetry or Karl-Fischer titration and moisture sorption/desorption analysis for hydrates. In order to perform studies... 

The moisture-solid interaction is an inevitable aspect of pharmaceutical development. Elucidation of moisture-induced physical alterations in amorphous pharmaceuticals is crucial, especially for ASD. Gravimetric measurement on the rate and extent of moisture gain (sorption) by or loss (desorption) from amorphous samples as a function of RH or as a function of time at a constant RH (isohumic condition) can provide a wealth of information of ASD. The key structural properties of ASD measureable by moisture sorption/desorption are drug-polymer interactions, moisture-induced glass transition, crystallization, hydrate formation/dehydration, etc. while that associated with particulate or bulk properties are hygroscopicity, diffusivity, pore size, surface area, etc. (Burnett et al. 2009). 

Figure 10. The enthalpy change for water vapor sorption determined as a function of RH using a RH perfusion device coupled with an isothermal microcalorimeter. Assuming a second order BET model, the enthalpy of moisture sorption was found to be 53.33 kJ mol" of water from 0 to 40% RH and 43.77 kJ mol" of water from 40 to 80% RH (close to the enthalpy change of vaporisation). The available surface area changed from 0.68 mg m to 0.72 mg m". The data suggest binding to the drug surface up to 40% RH then formation of multiple hydrate spheres above 40% RH.

Nonspecific hydration, or hydration of the lattice without first-order phase transitions, also must be considered. Cox et al. [40] reported the moisture uptake profile of cromolyn sodium, and the related effects on the physical properties of this substance. Although up to nine molecules of water per molecule of cromolyn sodium are sorbed into the crystalline lattice at 90% relative humidity, the sorption profile does not show any sharp plateaus corresponding to fixed hydrates. Rather, the uptake profile exhibits a gradual increase in moisture content as relative humidity increases, which results in... 

Hygro-themo-chemo-mechanical behaviour of concrete is of great practical importance in many fields of civil engineering. Modelling these phenomena, especially in fresh concrete structures or concrete elements exposed to fire, is a complex problem. Several non-linear phenomena, like heat and mass sources associated with hydration or dehydration processes, phase changes, hysteresis of sorption isotherms, material properties dependent on moisture content, tem-... 

Although some specific examples are given, several aspects of the sorption of water by crystalline substances deserve attention at this point. First, it is important to recognize that the large quantity of water that associates with these systems actually obscures small changes in moisture content that occur between hydrate transitions. It has been stated that lactose monohydrate, for example, contains 5 /o water of crystallization and approximately 0.1 /o adsorbed water ,indicating that adsorption takes place on the hydrate. 

For hygroscopic solids, the enthalpy of the attached moisture is less than that of pure liquid by an amount equal to this binding energy, which is also termed the enthalpy of wetting, A// , (Keey 1978). It includes the heat of sorption, hydration, and solution and may be estimated from the following equation ... 

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