Other environmental factors affecting stability

The stability of an oxidisable dmg in a liquid dosage form is generally a function of the efficiency of any antioxidant included in the formulation. Exaggeration of the effect of oxygen on stability may be achieved by an increase in the partial pressure of oxygen in the system. It is not often easy, however, to make decisions 

The stability of solid dosage forms is usually very susceptible to the moisture content of the atmosphere in the container in which they are stored (see section 4.4.3) A linear relationship between log k and the water vapour pressure for vitamin A palmitate beadlets in sugar-coated tablets has been found. Similarly, a linear relationship between the logarithm of the rate constant for the decomposition of nitrazepam in the solid state and the relative humidity has been established (Fig. 4.f9). The need for consideration of the effect of moisture on stability has been stressed by Carstensen, who stated that stability programmes should always include samples that have been artificially stressed by addition of moisture. One purpose of a stability programme should be to define the stability of the dosage form as a function of moisture content. 

---

Detrital processing can be thought of as a continuum from fresh litter to stabilized SOM (Agren and Bosatta, 2002). At different stages in this continuum, the relative importance of each of these environmental and biological factors that have been identified as controlhng decomposition dynamics will likely vary. The initial stages of mass loss are characteristically most affected by climate, resource quality, and, when abundant, soil macrofauna. The physical soil environment also needs to be considered as an important control on the turnover of more humified SOM in the mineral horizons. It is also evident from this literature review that observed correlations between decay rates and decomposition factors are often attributable to both the direct effects of that factor on microbial metabolism and to the indirect interactions with other factors. 

Other factors, such as lack of experience at the new site in a particular dosage form or difference in the environmental conditions between the sites, can potentially affect the quality or stability of a drug product. Therefore, one site-specific batch may not be sufficient in these cases. More than one site-specific batch may be needed for a drug substance or product that is intrinsically unstable. 

Despite the extensive mechanistic studies, there continues to be the need for more work. Many questions remain to be answered. For example, how do asymmetric environments affect the S Ar reaction What factors provide the highest regioselectivity in S Ar reaction When does the jc-complex form and how does it affect the S Ar reaction How does o-complex stability affect the outcome of these synthetic conversions Can electrophiles be generated that show unusual reactivities How do environmentally friendly catalysts affect the S Ar reaction mechanism These and other questions wiU certainly be addressed by research chemists in the decades ahead. 

---