Drug absorption surfactant effects

Surfactants have been explored widely for their effects on drug absorption, in particular using experimental animals (Gibaldi and Feldman, 1970 Gibaldi, 1976). Surfactants alter dissolution rates (of lipid materials), surface areas of particles and droplets, and membrane characteristics, all of which affect absorption. 

In some biological systems nonionic surfactants have an intrinsic biological activity the Ci2 alkyl ethers were too toxic to be used in the experiments of drug absorption with goldfish. The activity of the C12 ethers was quantified by measurement of the fish turnover time, T. When the reciprocal of the turnover time is plotted against alkyl chain length for the series Cx and Ejq and C12 compound is distinguished by its marked effect. (12). 

Surfactants have been the most investigated chemicals to promote drug absorption from all body tracts. In this section, we will focus on work carried out from the early stages on the enhancing effects of surfactants on drug GI absorption as well as on their interactions with the GI membrane and their toxicity. Systems with multifactorial effects such as emulsions and microemulsions are not the focus of this review. 

Gibaldi, M., and S. Feldman. 1970. Mechanisms of surfactant effects on drug absorption. J Pharm Sci 59 579. 

Utsumi, I., K. Kono, and Y. Takeuchi. 1973. Effect of surfactants on drug absorption. IV. Mechanism of the action of sodium glycocholate on the absorption of benzoylthiamine disulfide in the presence of sodium laurylsulfate and polysorbate 80. Chem Pharm Bull (Tokyo) 21 2161. 

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... 

Any enhancing effect of surfactants on drug absorption appears to be related to increased drug solubilization, modification of mucosal permeability, or reduction of resistance of the unstirred water layer at the GI membrane surface. In general, unionic surfactants have little effect on membrane structure but cationic surfactants have been associated with reversible cell loss and loss of goblet cells. These effects must limit consideration of surfactants as absorption promoters, particularly for long term treatment. 

Mixed micelles consist of fatty acids solubilized by surfactants or bile salts. The effects of mixed micelles on drug absorption were reviewed by Muranishi Mixed micelles are effective absorption enhancers for compounds such as heparin, streptomycin, gentamycin, and insulin. The effect of mixed micelles on drug absorption tends to be greater at the distal region of the GI tract. The mechanism for increased absorption is not known. Some publications claim that they are safe to use. Others report a disordering effect on intestinal epithelial cells. 

Numerous studies on the influence of surfactants on drug absorption have shown that they can increase, decrease or exert no effect on the transfer of drugs through membranes [14]. As discussed above, the presence of surfactant affects the dissolution rate of the drug, although the effect is less than predicted by the... 

Fig. 2.21 Schematic representation of the effect of surfactants on drug absorption and drug activity.

---