Excipients water content

Factors affecting the mix of active ingredients and excipients should be discussed. These should include particle size and shape, rugosity, charge, flow properties, and water content. Since the dose delivery for these products is dependent on air flow characteristics, an attempt should be made to establish an in vivo-in vitro correlation. 

The stability of moisture-sensitive drugs has been studied by Vromans and Schalks [1.143] using amorphous vecuronium bromide. Its decomposition in a formulation depends more on the water activity aw (see Chapter 4, point 2) than on the water content. Glass-forming excipients may not only be cryoprotective but also stabilizing. 

These beyond-use date limits may be exceeded when there is supporting valid scientific stability information that is directly applicable to the specific preparation (i.e., the same drug concentration range, pH, excipients, vehicle, water content, etc.)... 

Determination of physico-ehemical properties of drugs and excipients such as particle size, water content and polymorphism... 

Table 3—Residual amount of excipient and water content of remaining excipient in matrix after 16 days of release...

It is important to note that the overall purity of the material should be considered prior to investigation of excipient compatibility, such as starting impurity levels, levels of residual water content and residual solvents, as well as the presence and levels of heavy metal impurities. A consideration of the enantiomeric and diastereomeric purities of the materials should be given and may be correlated to instability noted in compatibility studies. 

Sometimes our method helped the pharmaceutical technicians to modify the formula of the excipients and stabilize the water content. They could also better understand the as-yet-unknown behavior of certain additives like heavy polyalcohols, glycerol, or tensioactive agents. 

The mechanism of the protective effects imparted by the excipients has not been fully elucidated. Empirical observations have pointed to the following contributing factors formation of a glassy state of the protein-excipient system crystallinity of the excipients hydrogen bonding between the excipient and protein molecules and residual water content. 

One of the main ways in which the excipients of the solid dosage form can affect the degradation of dmgs is by increasing the moismre content of the preparation. Excipients such as starch and povidone have particularly high water contents (povidone contains about 28% equilibrium moisture at 75% relative humidity). However, whether this high moismre... 

Similar behavior has been observed for noncrystallizing polymers. For example, the diffusivity of water in poly(vinylpyrrolidone) (PVP) (Oksanen and Zografi, 1993) has been shown to increase at water contents beyond the hydration limit. Additional reports have shovm that the hydration limit has physical significance for other polymer excipients. Microcrystalline cellulose and lactose for compression, for example, lose their direct compaction properties at water contents just below (Huettenrauch and Jacob, 1977), and gelatin capsules become brittle as the water content is reduced below Wm (Kontny and Mulski, 1989). Recently, the chemical stability of a model peptide in PVP matrices was shown to improve when the amorphous dispersion was stored below the polymer s hydration limit (Lai et al., 1999a Lai et al., 1999b Lechuga-Ballesteros et al., 2002). 

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