Effect of surfactants on drug absorption

In this section is reviewed a selection of the available evidence on this topic. Typical of the confusion that still exists is the conclusion arrived at in one paper [77] in which tetracycline, sulphanilamide, isoniazid and salicylic acid were used as test drugs and sodium lauryl sulphate, benzethonium chloride, polysorbate 80 and sucrose mono- and di-stearates as the surfactants. A perfusion technique involving the rat small intestine was employed. It was found that (i) the ionic nature of the surfactants substantially influenced the absorption (ii) the rate of absorption of tetracycline was accelerated by the presence of sodium lauryl sulphate, benzethonium chloride or sucrose esters (iii) polysorbate 80 caused a marked reduction in the absorption of salicylic acid and tetracycline  

Percent drug dissolved in the suspension dosage forms 

Absorption of normally non-absorbed or poorly absorbed water soluble drugs from a Thomas gastric fundic pouch of the dog is greatly increased by certain surfactants [83]. Vitamin B12 absorption from both stomach and intact gastrointestinal tract of the rat is similarly enhanced [84]. As might be anticipated, while blood levels of cephaloridine are elevated several fold when surfactant is added to the ligated stomach, their influence in the intact GI tract is diminished and 

From previous results, for example those of griseofulvin and dicoumarol suspensions, one might have predicted that addition of polysorbate 80 to a suspension of a poorly soluble anticonvulsant, a piperazine derivative with a solubility less than 0.1 mgml would have increased its bioavailability. But, responses in terms of the animal s protection from convulsant challenges was decreased by 0.8 % polysorbate 80 (Fig. 7.27). 

Recently, insulin absorption via the jejunum has been effected by administration of insulin-cetomacrogol solutions to diabetic rats [87]. Results presented in Table 7.5 are most likely to be due to a membrane effect rather than a surfactant-protecting effect on insulin degradation, as insulin administered h after cetomacrogol elicited a hypoglycaemic effect (see Section 7.4.2 below on rectal absorption). Sodium lauryl sulphate (0.75%) and sodium taurocholate (3.2 %) have been reported to cause an increase in the percentage of insulin absorbed from the ligated rat jejunal loop from 0.4% to 3.2% and 3.4%, 

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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. 

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. 

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

Such interactions are directly relevant to the effect of surfactants on drug absorption. Fig. 10.5a shows the relationship between absorption of salicylate or L-valine across rat jejunal tissue in vivo and release of protein and phospholipid by a series of surfactants. Fig. 10.5b shows the relative activity of a series of non-ionic surfactants of the Brij series and sodium taurodeoxycholic acid (NaTDC), sodium dodecyl sulphate (NaDS) and CTAB [30]. An association between protein release and increased absorption of solutes has also been reported by Feldman and Reinhard [31] and Walters et al. [32]. Anionic, non-ionic and cationic surfactants tended to accelerate the breakdown of the mucous layer covering the epithelium and at high concentrations were thought to interfere with the structure of the mucosal surface itself. Exposure of various anionic and nonionic surfactants to rabbit intestinal mucosa causes epithelial desquamation and necrosis [33]. 

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. 

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... 

Gouda, M.W., N. Khalafalah, and S.A. Khalil. 1977. Effect of surfactants on absorption through membranes V Concentration-dependent effect of a bile salt (sodium deoxycholate) on absorption of a poorly absorbable drug, phenolsulfonphthalein, in humans. J Pharm Sci 66 727. 

Sekine, M., et al. 1985. Improvement of bioavailability of poorly absorbed drugs. V. Effect of surfactants on the promoting effect of medium chain glyceride for the rectal absorption of (3-lactam antibiotics in rats and dogs. J Pharmacobiodyn 8 653. 

Hirai, S., Yashiki,T., and Matsuzawa,T., Nasal absorption of drugs. Effect of surfactants on the nasal absorption of insulin in rats, paper presented at the 98th annual meeting of the Pharmaceutical Society of Japan, Apr. 1978. 

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. 

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

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. 

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