Surfactants permeation enhancers

Pharmaceutical scientists assess and express drug permeation across membrane barriers in terms of flux. Flux measures the molar unit of a drug that permeates a resistant barrier (e.g., skin or gastrointestinal epithelial cells) per unit time and surface area (Box 13.1). Permeation enhancers, such as alcohols and surfactants, increase flux by modulating resistance factors that counteract drug diffusion across barriers at the site of administration. 

The enhancement of insulin absorption by sodium caprate (Ci0) in a closed loop model in rats showed the following rank of efficiency colon > ileum > jejunum > duodenum. On the other hand, sodium glycocholate affected the intestinal permeability in a different way. With this surfactant, the order of permeation enhancement was colon > jejunum > duodenum > ileum [95], These results show that the absorption site in the GI tract may strongly affect the effectiveness of permeation enhancer. 

The ideal permeation enhancer is safe, effective, pharmacologically inactive, chemically inert, and has a reversible effect (does not compromise the mucosal barrier function for extended periods) [10]. It is noticeable that the majority of the most widely investigated permeation enhancers have surfactant-like properties, and those that are water soluble seem to be most active at concentrations above the critical micelle concentration. The following have been investigated as a means of enhancing buccal permeability. 

Azone (laurocapram) is used extensively as a transdermal permeation enhancer, and has also found use in buccal drug delivery. It is a lipophilic surfactant in nature (Figure 10.4). Permeation of salicylic acid was enhanced by the pre-application of an Azone emulsion in vivo in a keratinized hamster cheek pouch model [35]. Octreotide and some hydrophobic compounds absorption have also been improved by the use of Azone [36], Azone was shown to interact with the lipid domains and alter the molecular moment on the surface of the bilayers [37], In skin it has been proposed that Azone was able to form ion pairs with anionic drugs to promote their permeation [38],... 

FIGURE 10.5 Some examples of surfactants used as permeation enhancers. 

Low molecular mass permeation enhancers include numerous classes of compounds with diverse chemical properties including detergents, surfactants, N-acetylated x-amino acids, N-acetylated non-a-amino acids, fatty acids, medium-chain mono- and diglycerides, acyl carnitine, alkanoyl cholines, Ca2 + chelating agents, zonula occludens toxins and NO donors. 

Some of these low molecular mass permeation enhancers act as surfactants/ detergents to increase the transcelluar transport of more lipophilic drugs by disrupting the structure of the lipid bilayer and rendering the cell membrane... 

Swenson ES, Milisen WB, Curatolo W (1994) Intestinal permeability enhancement structure-activity and structure-toxicity relationships for nonylphenoxypolyoxyethylene surfactant permeability enhancers. Pharm Res 11 1501-1504 Tomita M, Hayashi M, Horie T, Ishizawa T, Awazu S (1988) Enhancement of colonic drug absorption by the transcellular permeation route. Pharm Res 5 786-789 Tomita M, Sawada T, Ogawa T, Ouchi H, Hayashi M, Awazu S (1992) Differences in the enhancing effects of sodium caprate on colonic and jejunal drug absorption. Pharm Res 9 648-653... 

Transcellular permeation enhancers include surfactants, medium chain fatty acids, nonionic surfactants,38 sodium cholate and other bile salts,39 and many other surfactants. 

DSC studies supported this result shov g lipid transitions in die imtreated rat SC at 41.9, 55.1, 70.2, and 77.5 °C, while SC pre-treated with disodium hydrogen phosphate and ibuprofen showed only the last lipid transition. This confirms that ibuprofen disrupts the SC and, through its ability to act as an anionic surfactant, gives rise to self permeation enhancement [12],... 

Sprays are liquid dosage forms aerosolized into the oral cavity for transmucosal drug delivery. Due to the formation of small droplets upon aerosolization of the liquid, sprays can achieve shorter lag times and a faster onset of action than other liquid formulations. Oral-lyn is a micellar system utilizing a blend of surfactants as permeation enhancers and formulation stabilizers. The product is one application of the RapidMist system patented by Generex Biotechnology Corporation that has also been used to develop products for vaccine delivery, pain management, and weight loss. 

Uses Surfactant, emulsifier, coemulsifler, stabilizer, wetting agent, lubricant, plasticizer, emollient, solvent, and antistat in cosmetics, pharmaceuticals, foods, industrial applies., pulp/paper, metalworking, lubricants, textiles, agric., paints, adhesives food additive, defoamer pharmaceutical emulsifier, stabilizer, lubricant, solvent, excipienL permeation enhancer in food-pkg. adhesives Regulatory FDA 21CFR 172.856,173.340,175.105,175.300,176.170, 176.210,177.2800... 

These phases are (a) thermodynamically stable (b) consist of nano-scaled hydrophilic and hydrophobic domains, which are separated by the surfactant self-assembled layers (c) contain an extremely large surface and present the ability to incorporate compounds independent of their solubility, to protect them from physical and enzymatic degradation, and to sustain their delivery and (d) may consist of permeation enhancers as the structure-forming hpid/solvent [54, 61]. 

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