Excipient hygroscopicity

The three hygroscopic excipients used were citric acid anhydrous, sorbitol, and maltodextrin. It was found that hygroscopic materials do not markedly increase the adsorption of atmospheric moisture by a tablet until high relative humidities were attained. 

Polyethylene glycol (PEG), a hygroscopic polymer, was the first molecule to be considered for modifying the surface of proteins. It has proved to be very successful. PEG, available in molecular weights ranging from a few hundred to several thousand daltons, have been used as parenteral excipients for decades with proven clinical safety. 

Establish the compatibility of the capsule shell and the capsule contents. Determine the hygroscopic nature of the capsule formulation. For example, a hygroscopic formulation (active ingredient and/or excipients) can pull water from the capsule shell, which could affect the Active ingredient—stability issues such as degradation and morphology changes... 

Some excipients contain a certain amount of amorphous form such as spray-dried lactose,27 and others are hygroscopic, such as microcrystalline cellulose.28 These excipients will adsorb water, which causes a change in the micro-environment of the formulation. If the drug substance is moisture-sensitive, degradation may occur quickly. Therefore, consider both drug-excipient compatibility and excipient impurity profile in selecting excipients for low-dose drug products. 

Most commercial ODTs have been developed using mannitol as the bulk excipient of choice because of its extremely low hygroscopicity, excellent compatibility, good compressibility, better sweetness, and relatively slower dissolution kinetics. Although lactose also has a relatively low aqueous solubility compared with other excipients that have acceptable palatabilities, the dispersibility of a bulk excipient is more important than its aqueous solubility for a successful ODT formulation. Many of the initially marketed ODTs were prepared by the wet granulation of mannitol followed by direct compression. However, added functionality mannitols are now available to simplify the process of ODT manufacturing by direct compression. 

The hygroscopicity of a drug and pharmaceutical substances is a potential parameter to be considered in tablet formulation. The moisture uptake rate is quite variable depending on the type of drug and excipients as well as the environmental conditions. So, a concise definition of hygroscopicity is not possible. Powders can absorb moisture by both capillary imbibition and swelling. The instantaneous water absorption prosperties of pharmaceutical excipients correlate with total surface area while the total absorption capacity correlates with powder porosity [22],... 

Depending on the hygroscopicity based on the EMC, various drug and excipients are classified in four groups (Table 16). 

Figure 8 also shows an example of moisture uptake for four selected excipients as a function of relative humidity. Depending on the hygroscopicity of the exscipi-ents, the uptake behaviors are quite variable. Excipients such as microcrystalline cellulose (MCC) and starch can pick up significant amounts of water at relatively low relative humidity. Since this water is not present as a hydrate, it is potentially free to interact with a drug. 

TABLE 16 Classification of Hygroscopicity and Example Pharmaceutical Excipients... 

The influence of sorbed moisture on chemical stability and the flow and compaction of powders and granulations is well established. The moisture content and hygroscopicity of excipients is particularly important as total product processing as well as finished product stability can be affected. Hygroscopicity, moisture-sorption isotherms, and equilibrium moisture content can be determined by thermogravimetric analysis and Karl Fisher titration methods. 

Mannitol is an isomer of sorbitol. Like the latter, it has a negative heat of solution which makes it a useful excipient for chewable tablets and lozenges. It is less hygroscopic than sorbitol and has about one-tenth of the solubility in water. Similarly to sorbitol, several polymorphic forms are available which differ in their ability to form tablets. " However, unmodified mannitol cannot be used for direct compression because of poor flow and binding properties. Directly compressible forms are available in a range of particle sizes which are reported to produce excellent tablets. 

The preformulation includes the choice of the salt form and of the polymorph of the drug substance. Melting points, solubilities, dissolution, hygroscopicity, stability, feasibility, processability, and polymorphic behavior have to be considered. The second step is to study the behavior of the drug substance with excipients. ° ... 

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