complexes part5

Complexes of testosterone with amorphous hydroxypropyl ?-cyclodextrin allow an efficient transport of hormone into the circulation when given sublingually. This route avoids both metabolism of the drug in the intestines and rapid first-pass decomposition in the liver, thus improving bioavailability.
In addition to hydrophilic derivatives, hydrophobic forms of ?-cyclodextrin have been found useful as sustained-release drug carriers. Thus, the release rate of the water-soluble calcium antagonist, diltiazem was significantly decreased by complex¬ation with ethylated ?-cyclodextrin. The release rate was controlled by mixing hydrophobic and hydrophilic derivatives of cyclodex¬trins at several ratios. Ethylated ?-cyclodextrin has also been used to retard the delivery of isosorbide dinitrate, a vasodilator.
Cyclodextrins may improve the organoleptic characteris¬tics of oral liquid formulations. The bitter taste of suspen¬sions of femoxetine, an antidepressant, is greatly suppressed by complexation of the drug with ?-cyclodextrin .
Molecular sieves
Macromolecular inclusion compounds, or molecular sieves as they are commonly called, include zeolites, dextrins, sil¬ica gels, and related substances. The atoms are arranged in three dimensions to produce cages and channels. Synthetic zeolites may be made to a definite pore size so as to separate molecules of different dimensions, and they are also capa¬ble of ion exchange.
Methods of analysis
A determination of the stoichiometric (the quantitative relationships that exist between the reactants and products in chemical reactions) ratio of ligand to metal or donor to acceptor and a quantitative expression of the sta¬bility constant for complex formation are important in the study and application of coordination compounds. A limited number of the more important methods for obtaining these is quantities is presented here.
Method of continuous variation
Suggestion for the use of an additive property such as the spectrophotometric extinction coefficient (dielectric constant or the square of the refractive index may also be used) was made for the measurement of complexation. If the property for two species is sufficiently different and if no interaction occurs when the components are mixed, then the value of the property is the weighted mean of the values of the separate species in the mixture. This means that if the additive property, say di¬electric constant, is plotted against the mole fraction from 0 to 1 for one of the components of a mixture where no com¬plexation occurs, a linear relationship is observed, as shown by the dashed line in Figure 11-7. If solutions of two species A and B of equal molar concentration (and hence of a fixed total concentration of the species) are mixed and if a com¬plex forms between the two species, the value of the additive property will pass through a maximum (or minimum), as shown by the upper curve in Figure 11-7. For a constant total concentration of A and B, the complex is at its greatest concentration at a point where the species A and B are com¬bined in the ratio in which they occur in the complex. The line therefore shows a break or a change in slope at the mole fraction corresponding to the complex. The change in slope occurs at a mole fraction of 0.5 in Figure 11-7, indicating a complex of the 1:1 type.