Local anaesthetics surface activity

The presence of hydrophilic and hydrophobic regions in the same molecule is not a monopoly of surfactants most drug molecules feature hydrophilic and hydrophobic regions as well, and this is indeed the structural requirement for their ability to permeate cell membranes and pass absorption barriers. The amphiphihc properties are obvious in some drug classes, e.g. the local anaesthetics. On some occasions a drug substance may exceed the CMC, whereupon micellar self-solubilization can occur. A recent example was described by Hussain and coworkers who found that the hydrochloride of the basic analgesic DuP 747 is surface active the saturated solution (3 mg ml - at 22°C) lowered the surface tension of water to 50dyncm. It was hoped... 

It is a local anaesthetic of the amide type which is employed for surface, infiltration and nerve block anaesthesia. Its duration of action is in between the shorter-acting lidocaine and longer-acting mepivacaine. It possesses less vaso-dilator activity than lidocaine and hence may be used without adrenaline. Therefore, solutions of prilocaine hydrochloride are specifically beneficial for such patients who cannot tolerate vasopressor agents patients having cardiovascular disorders, diabetes, hypertension and thyrotoxicosis. 

Many other excipients and active substances that are mainly used for another purpose, also exhibit surface activity. Examples can be found in the group of viscosity enhancing substances (see Sect. 23.7). In particular the low viscous methylceUulose is used for this purpose. Examples of active substances that have surface activity are the tricyclic antihistaminics and antidepressants, and the local anaesthetics (e.g. Udocaine). 

Many local anaesthetics have significant surface activity and it is tempting to correlate their surface activity to their action. However, one should not forget other important factors such as partitioning of the drug into the nerve membrane (a factor that depends on the pfCa) and the distribution of hydrophobic and cationic groups, which must be important for the appropriate disruption of nerve membrane function. 

The accumulation effect can be exploited also for adsorptive stripping analysis of polarographically reducible surface active compounds. As an example, the local anaesthetic Percaine Ciba (Table 1) can be mentioned the obtained peak belongs to the reduction of the adsorbed compound (Figure 3). Other examples of adsorptive accumulation of electroactive compounds are the Ge (Figure 5) and Cu surface active complexes mentioned in Table 1. In the case of the adsorbable complexes mentioned the method is suitable mainly for metals where the amalgam formation is complicated or where the solubility of the metal in mercury is low. 

Surface activity and colloidal properties of drugs 153 4.1.9 Local anaesthetics... 

The surface activity of local anaesthetics has been measured by several workers [102,103] in attempts to relate surface properties to local anaesthetic action (see Section 4.2.4). The penetration of monolayers formed from lipids extracted from... 

Figure 4.23 Variation of local anaesthetic potency with surface activity of compounds. Local anaesthetic potency (ordinate) is expressed as mean molar potency (relative to procaine hydrochloride = 1) as determined in guinea-pig intradermal weal test. Surface activity (abscissa) is expressed as concentration (mmol P ) required to reduce the surface tension of water to 60 mN m The five series of compound are shown as follows ...

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