Drug solubility complexation

Fig. 15.1. Factors limiting oral drug absorption. Dissolution and the aqueous drug solubility in the gastrointestinal fluids are two of the properties influencing oral drug absorption. When the drug is in solution, it can be subjected to chemical degradation and complex binding with components of the gastrointestinal fluids and/or be metabolised by...

The solubility of a drug candidate may not always be sufficient for its intended pharmacological purpose, and in such cases the solubility may need to be modified (either increased or decreased). These concerns are especially important for parenterals when the active substance does not exhibit the desired level of solubility. The solubility of a given compound can be profoundly altered in a number of ways, such as through the formation of salt species or drug-substrate complexes, or through the use of surfactants or cosolvents [43], In the majority... 

The computation of formation constants is considered to be the most important aspect of equilibrium theory, since this knowledge permits a full specification of the complexation phenomena. Once this information is in hand, the formulator can literally define the system at a given temperature through the manipulation of solution-phase parameters to obtain the required drug solubility. 

Figure 5 Effect of drug solubility on drug release from drug-PDADMAC complex tablets at pH 7.0 (0.2 M NaCl). 

Poisoning - Penicillamine also forms soluble complexes with iron, mercury, lead, and arsenic, which are readily excreted by the kidneys. The drug may be used to treat poisoning by these metals. 

Whether we discuss silk, proteins embedded in membranes, or soluble complexes of cytosolic proteins, we must ask questions about interactions. A first step is to identify interactions720-730 among proteins either in vitro or in living cells.731 Proteomic methods, which include the yeast two-hybrid method (Box 29-F), are widely used for this purpose. It is possible to identify large sets of interacting proteins, to identify disease states, to observe effects of drugs, and to compare metabolism among species. 

Phase-solubility diagrams are frequently used to calculate stoichiometry of drug/CD complexes. 

Solubilization of poorly water-soluble drugs by complexation with cyclodextrins and then delivery via the buccal or sublingual mucosa has been studied as an additional strategy for increasing drug absorption. Cyclodextrins are able to form inclusion complexes with drugs,... 

FIGURE 6 Representation of drag in-cyclodextrin in liposome technique for encapsulation of lipophilic drugs in aqueous interior of vesicles. Drag molecules have low aqueous solubility and thus cannot be encapsulated in the aqueous compartment of the vesicle. However, the drug-cyclodextrin complex has high aqueous solubility and can thus be encapsulated in high concentrations in the vesicles. 

Complexation Drug is entrapped or complexed with excipients that can mask the lipophilic groups of the drug and enhance drug solubility in water. Cyclodextrins are commonly used to entrap hydrophobic drugs in the core, while the hydrophilic groups on the periphery help to solubilize the drug. 

Double Antibody Technique. Although the drug-antibody complex is large it is still soluble. It can be converted into an insoluble form, which can be centrifuged, by the addition of a second antibody (the precipitating antibody) raised against the globulins of the animal in which the first antibody was raised. The free fraction is then simply decanted out of the tube. 

---