Absorption enhancers nonionic surfactants

In 1978, two papers, one from Israel and one from Japan, published in the same issue of the Journal of Pharmacy and Pharmacology reported successful rectal insulin absorption by use of polyoxyethylene (POE) ether nonionic surfactants [59,60], These reports led to further investigations on the use of surfactants for enhancing the absorption of macromolecules. Later in this chapter we will discuss the work done on the enteral delivery of large molecules with nonionic and anionic promoters, which have been the most investigated ones to date. 

Sakai, K., et al. 1986. Contribution of calcium ion sequestration by polyoxyethylated nonionic surfactants to the enhanced colonic absorption of p-aminobenzoic acid. J Pharm Sci 75 387. 

A simple, rapid, sensitive, and selective spectrofluorimetric method (2ex/ lem = 345/455nm) has been developed for the determination of zaleplon. Tang et al. have studied the influence of micellar medium on the absorption, fluorescent excitation, and emission spectra character of zaleplon The nonionic surfactant of Triton X-100 showed a strong sensitizing effect for the fluorescence of zaleplon in a pH 5.0 buffer. The possible enhancement mechanism was discussed. Based on the optimum conditions, the linear range was 1.32 x 10 8-1.00 x 10 mol/1. The detection limit was 4.0 x 10 mol/1 with a relative standard deviation (RSD) of 0.06%. The proposed method was successfully applied to the determination of zaleplon in tablets, serum, and urine. 

Rivera TM, Leone-Bay A, Paton DR, Leipold H, Baughman RA (1997) Oral delivery of heparin in combination with sodium N-[8-(2-hydroxybenzoyl) aminojcaprylate pharmacological considerations. Pharm Res 14 1830-1834 Sakai K, Kutsuna TM, Nishino T, Fujihara Y, Yata N (1986) Contribution of calcium ion sequestration by polyoxyethylated nonionic surfactants to the enhanced colonic absorption of p-aminobenzoic acid. J Pharm Sci 75 387-390 Sakai M, Imai T, Ohtake H, Azuma H, Otagiri M (1997) Effects of absorption enhancers on the transport of model compounds in Caco-2 cell monolayers assessment by confocal laser scanning microscopy. J Pharm Sci 86 779-785... 

A systematic study in rats, in which the absorption-enhancing effects of a number of surfactants were compared, was reported by Hirai et al (1981a,b). The promoting effect of several nonionic surfactants was paralleled by their ability to lyse red blood cells and to release protein from the nasal mucosa of rats. Bile salts, however, were found to be less lytic and damaging to the rat nasal mucosa than nonionic ether-type surfactants. Generally, a positive correlation was observed between the damaging effect on the biomembrane and the absorption-promoting effect of the surfactants. 

Poly(ethylene oxide)/Poly(propylene oxide)/ Poly(ethylene oxide) Triblock Copolymer Pluronic is a trade name for poloxamers, which are nonionic triblock copolymers of PEO chains on the two ends of the molecules with a poly(propylene) oxide (PPO) chain in the middle. The PEO chain is hydrophilic, while the PPO chain is hydrophobic. The polymer properties can be tailored depending on the content ratio of the constituents. Due to the combined hydro-phobic and hydrophilic properties in the structure (amphiphilic), it can be used as a stabilizer and a surfactant. It also can enhance miscibility and water absorption of polymers, and it has low toxicity itself. Pluronic has been used in drug delivery devices for controlled release purposes [220]. 

In addition to their adverse effects on the skin barrier properties, surfactants also are used to enhance the penetration of active ingredients into the skin [149]. When used in this fashion, the surfactant is known as a penetration enhancer. Of the three classes of surfactants, the nonionics, because of their low irritancy potential, have received the most attention. However, Maibach and co-workers [150,151] have investigated the effects of sodium lauryl sulfate on the percutaneous absorption of hydrocortisone, indomethacin, ibuprofen, and acitretin. 

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