Excipient moisture level

Changes in the moisture level of the excipient owing to the change. 

Water is often used in the process of preparing dosage forms. For example, lyophilization involves the dissolution or dispersion of a drug and excipients in water, freezing of the mixture and removal of the water by sublimation. The residual moisture level in lyophiles is typically 1-5% by weight, an amount adequate to induce chemical instability with a number... 

For lyophilized dosage forms, there is sometimes an optimum moisture content for stability, especially for proteins. The choice of excipient can determine the moisture content of the lyophilized cakes based on the moisture sorption levels.12 Controlling moisture levels to this optimum also requires that the dosage form be protected from environmental moisture, usually by packaging in glass. 

Li et al. [27] used NIR spectroscopy to troubleshoot and optimize a wet granulation process. During development phases, authors realized that out-of-trend content uniformity values were obtained for some sieve cuts due to the interaction of the excipients and the binding solution during the coalescence process. A qualitative method was put in place to determine within different sieve fractions the change in content uniformity. Other process optimization methods involving NIR were described by Miwa et al. [28-30]. They used moisture levels predicted by NIR for independent components to estimate a lower and an upper limit for the amount of water needed to granulate a multicomponent system. 

The original applications of NIR were in the food and agricultural industries where the routine determination of the moisture content of foodstuffs, the protein content of grain and the fat content of edible oils and meats at the 1% level and above are typical examples. The range of industries now using the technique is much wider and includes pharmaceutical, polymer, adhesives and textile companies. The first in particular are employing NIR spectrometry for the quality control of raw materials and intermediates and to check on actives and excipients in formulated products. Figure 9.26(b) demonstrates that even subtle differences between the NIR spectra of enantiomers can be detected. 

Crowley and Martini [48] reported on several studies evaluating the impact of unit process operations on hydrates. AU showed some level of dehydration liberating freed crystalline water to participate in moisture-mediated reactions. The authors speculated that such energetic processing conditions are likely to have a similar affect on hydrated excipients with a potential deleterious effect on moismre-sensitive APIs. They commented that classical excipient compatibility studies were ill-equipped to predict such moismre-mediated interactions and that compression, attrition and other energy-intensive unit operations were rarely mentioned as requiring investigations. 

Calcium sulfate dihydrate is used as an excipient in oral capsule and tablet formulations. At the levels at which it is used as an excipient, it is generally regarded as nontoxic. However, ingestion of a sufficiently large quantity can result in obstruction of the upper intestinal tract after absorption of moisture. 

When excipients and dosage forms are exposed to various humidity conditions, water vapor sorption will occur. The relative water vapor sorption levels for a number of excipients have been studied.2 It was found that the total water vapor sorption in solid dosage forms can be predicted from the individual contributions of the excipients as powders. The moisture sorption tendency of an excipient will not only depend on the chemical nature of the excipient, but also on the particle size.3 Because of these effects, without packaging protection, water sorption can be significant for a number of dosage forms. 

The variable properties of solids are coimected with the ability of molecules to exist in different states of order, ranging from closely packed molecular crystals with a minimum free energy to metastable crystal phases and, finally, to the glassy state with the highest free energy. This phenomenon is commonly referred to as polymorphism. Lattice defects in crystals and particularly solvate formation add another level of complexity. Whether a solid in any metastable state can be handled and analysed is a kinetic issue, which again is affected by many factors (e.g. chemical impurities, solvent residues, moisture, and interactions with drug excipients). 

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