Structure XV Polyethylene glycol esters of indometacin identified in stored suppositories (n = number of ethylene oxide units)

phenolic impurities in tablet binding agents such as povidone, disintegrants such as crospovidone and viscosity-modifying agents such as alginates can lead to photodegradation. Similarly, coloured products may be formed by the reaction of aldehydes formed during spray-drying or autoclaving of lactose with primary amine groups in the product.


The effect of temperature change on the stability of solid dosage forms can be complicated for many possible reasons. The drug or one of the excipients may, for example, melt or change its polymorphic form as temperature is increased, or it may contain loosely bound water which is lost at higher temperatures. We should also remember that the relative humidity will change with temperature and so we must take care to keep this at a constant value.

Despite these possible complications, many authors have found that the effect of temperature on decomposition rate can be described by an Arrhenius-type equation; i.e. plots of log k against 1/T are linear. This then enables the stability to be predicted at room

Cl temperature from measurements made at elevated temperatures. Also, of course, we can calculate an apparent activation energy, Ea, from the gradient of the plots, but we must remember that this does not have the same meaning as the activation energy for reactions in solution. The Ea value in the solid state is affected, for example, by changes not only in the solubility of the drug in the moisture layer but also in the intrinsic rate of reaction. We cannot, however, use the Arrhenius equation in cases where decomposition shows an approach to equilibrium. Examples of such systems include vitamin A in gelatin beadlets and vitamin E in lactose base tablets. In these cases we can often use the van't Hoff equation to describe the effect of temperature on breakdown. We determine the equilibrium concentrations of products and reactants at a series of temperatures and then plot the logarithm of the equilibrium constant K against the reciprocal of the temperature (see Fig. 4.17) according to the equation

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