Surface Activity and Colloidal Properties of Drugs

Many drugs are surface active, e.g. chlorpromazine, diphenylmethane derivatives (such as diphenhydramine) and tricyclic antidepressants (such as amitriptyline) [14]. As an illustration is the structure of chlorpromazine (13.3). 

The biological and pharmaceutical consequences of the surface activity will be discussed here. The solution properties of these surface active drugs and their mode of association play an important role in their biological efficacy. 

Surfactants are also used in many pharmaceutical formulations, e.g. to prepare suspensions or emulsions of insoluble drugs, or as solubilizers (in the micelles) for many compounds for application as injectables or enhancement of the drug efficacy. Many surfactants are also used as germicides or antibacterials (e.g. the cationic quaternary ammonium salts). 

Another important class of surfactants is the bile salts (that are synthesized in the liver), phospholipids and cholesterol, which are the main constituents of membranes. These naturally occurring surfactants will also be discussed, briefly, in this section. 

The results of Fig. 2.15 clearly show distinct inflection points which may be identified with the critical micelle concentration (cmc). However, the aggregation numbers of these association units are much lower (in the region of 9-12) than those encountered with micellar surfactants (which show aggregation numbers of 50 or more depending on the alkyl chain length). These lower aggregation numbers cast some doubt on micelle formation and a continuous association process may be envisaged instead. 

The light scattering results could be fitted by Attwood and Udeala [14] using the mass action model for micellization. 

Considering the ionic micelle, to be formed by association of n drug ions, D,  

The equilibrium constant for micelle formation assuming ideality is given by the equation 

The standard free energy of micellization per mole of monomeric drug is given by 

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Surface activity and colloidal properties of drugs and naturally occurring substances... 

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