Surface activity, of drugs

The surface activity at the air/solution interface has been reported for a wide variety of dmgs. This surface activity is a consequence of the amphipathic namre of the dmgs. The hydrophobic portions of the dmg molecules are in general more complex than those of typical surfactants, often being composed of 

As with typical surfactants, the surface activity depends on the nature of the hydrophobic and hydrophilic portions of the drug molecule. The presence of any substituents on the aromatic ring systems can have an appreciable effect on hydrophobicity. Fig. 6.5 shows the decrease of cmc and increased surface activity 

Reproduced from D. Attwood and O. K. Udeala, J. Pharm. Pharmacol., 27, 754 (1975) with permission. 

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Considering the surface activity of drugs, as well as its consequences, e.g. for the interaction between the... 

Due to the surface activities of drugs, as well as the influence of interfacial interactions on the structure and stability of colloidal and self-assembled systems, the presence of the drug is frequently found to affect both the types of structure formed and their stabilities. This is of great importance, since it means that the properties of the drug must be considered in the design of the drug carrier, irrespective of the carrier being an emulsion, a microemulsion, a micellar solution, a liquid crystalline... 

There has been considerable recent interest in the self - assembly and surface activity of amphiphilic polymers and copolymers. Their interfacial and bulk solution properties have shown a rich pattern of behavior, and the ability to tailor their properties offers a wide range of potential applications. Their bulk aggregation behavior make them candidates, for example, for dye transportation and drug delivery whereas their surface properties make them useful as colloid stabilisers, anti -foaming agents and emulsifiers. This behavior can be illustrated in Fig. 3.24. 

Because the biological action of phenothiazine drugs may be due, at least partly, to their interaction with cell membranes, the study of adsorptivity and surface activity of phenothiazines has been carried out by several research groups. 

In this chapter we will see how the surface activity of a molecule is related to its molecular structure and look at the properties of some surfactants which are commonly used in pharmacy. We will examine the nature and properties of films formed when water-soluble surfactants accumulate spontaneously at liquid/air interfaces and when insoluble surfactants are spread over the surface of a liquid to form a monolayer. We will look at some of the factors that influence adsorption onto solid surfaces and how experimental data from adsorption experiments may be analysed to gain information on the process of adsorption. An interesting and useful property of surfactants is that they may form aggregates or micelles in aqueous solutions when their concentration exceeds a critical concentration. We will examine why this should be so and some of the factors that influence micelle formation. The ability of micelles to solubilise water-insoluble drugs has obvious pharmaceutical importance and the process of solubilisation and its applications will be examined in some detail. 

Surface area is important in all applications where the process is surface-dependent like in mass and heat transfer, flow through packed beds or fluidization. Activity of drugs, setting time of cement and effectiveness of cracking catalysts are just three examples of direct dependence on specific surface. Some such materials, like fillers or catalysts, are often specified in units of specific surface rather than in particle size and its distribution. Specific surface also offers some practical advantages, in favourable cases, in the ease and speed of measurement and also in that it gives a... 

A foam is a dispersion of a gas in a liquid or a solid. The formation of foam relies on the surface activity of the surfactants, polymers, proteins, and colloidal particles to stabilize the interface. Thus, the foamability increases with increasing surfactant concentration up to critical micelle concentration because above critical micelle concentration, the unimer concentration in the bulk r ains nearly constant. The structure and molecular architecture of the foam is known to influence foam-ability and its stability. The packing properties at the interface are not excellent for very hydrophilic or very hydrophobic drug. The surfactant promoting a small spontaneous curvature at interface is ideal for foams. Nonionic surfactants are the most commonly used one. The main advantage with foams is its site-specific delivery and multiple dosing of the drug. ... 

Several other examples may be quoted to illustrate the importance of surface activity of many drugs. Many drugs produce intralysosomal accumulation of phospholipids, which are observable as raultilamellar objects within the cell. Drugs implicated in phospholipidosis induction are often amphipathic compounds [20]. Interaction between the surfactant drug molecules and phospholipid renders the phospholipid resistant to degradation by lysosomal enzymes, resulting in their accumulation in cells. 

Interfadal Separation of Particles. By S. Lu, R.J. Pu and E. Forssberg Surface Activity in Drug Action. By R.C. Srivastava and AN. Nagappa... 

Uptake of paraquat by rat lung slices was found to be inhibited by chlorpromazine and efflux of paraquat from the slices was enhanced by the drug in vitro. However, in vivo chlorpromazine potentiated the toxicity of paraquat rather than reducing it as expected [187]. The metabolism of CPZ in vivo may account for the unexpected findings, although the decreased surface activity of some of the metabolites might be expected to give rise to a decreased membrane interaction. The increased toxicity was ascribed to reduced urinary excretion of paraquat and its increased pulmonary levels in the presence of CPZ, by mechanisms as yet not understood. 

Saccharin sodium produces qualitatively similar results yet is not known to be a surfactant ion [123]. At pH 7.4 NaLS has been found to increase the binding of ephedrine and quinine to rectal mucosal preparations by an unknown mechanism. It is presumed that Kakemi et al. [122] propose that the evidence of increased affinity for mucosal tissue signifies an increased concentration gradient of the drug at the interface but this is a concept that requires much more data and experimental evidence before being acceptable. The increased surface activities of the ion-pair may be a factor in increasing the interfacial concentration of the drug... 

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