Surfactants suppositories

Older compilations about the state of the art can be found in several review articles [41 -47]. It is surprising that most work is carried out with the surfactant bis-ethylhexyl-sulfosuccinate (tradename AOT or Aerosol OT). The reasons seem to be the variability of the obtained reverse micelles (from very low up to high water concentrations) and the well-known phase behaviour of AOT with water and several oils [48,49]. AOT is approved for medical application, e.g. as an additive in suppositories, but not for food engineering. 

Rectal absorption of drugs from aqueous or alcoholic solutions is generally much faster than from suppositories. Non-surfactant adjuvants, such as salicylates, increase rectal absorption of water-soluble drugs and also of high molecular weight compounds, such as insulin, heparin, and gastrin. 

Several non-ionic surface-active materials have been developed as suppositories vehicles. Many of these bases, known as water-dispersible bases, can be used for the formulation of both water-soluble and oil-soluble drugs. The surfactants most commonly used are thepolyoxyethylene sorbitan fatty acid esters (Tweens), the polyoxyethylene stearates, and the sorbitan fatty acidesters (Spans). These surfactants may be used alone, blended, or with other suppository base materials to yield a wide range of melting points and consistencies. 

Surface-active agents are widely used in combination with other suppository bases. The inclusion of these agents in the formulation may improve the wetting and water-absorption properties of the suppository. In addition, emulsifying surfactants help to keep insoluble substances suspended in a fatty base suppository,... 

The inclusion of a surfactant in the suppository formulation may enhance the rectal absorption of drugs. The effect has been attributed to the formation of mixed micelles. It has been suggested that the presence of the micelle facilitates the incorporation of the lipid component of the mixed micelle into the biological membrane. This lipid then enhances the fluidity and permeability of the membrane to the poorly absorbed drug. It appears that the colorectal mucous membrane is more sensitive to the effects of mixed micelles than the gastrointestinal membrane of the small intestine. 

El Assasy AH, Foda NH, Badawi SS, Abd-El-Rehim RT. Release characteristics and bioavallability of pirprofen from suppository bases. Egyptian ] Pharm Sci 1995 36(1-6) 15-29. Harmia-Pulkkinen T, Ojantakanen S. In vitro release kinetics of timolol and tlmol oleate from polyethylcyanoacrylate nanoparticles. Part 2. Nanoparticles manufacture with timolol maleate using different surfactants and organic solvents. Acta Pharm Penn 1992 101(2) 57-63. 

Drug Interactions and Availability - The role of surfactants in modifying the availability and/or the absorbability of various barbiturates via the rectal route was the subject of a report by Fincher, Entrekin, and Hartman.These workers, employing a petrolatum-paraffin base suppository, added various surfactants of known HLB values, and determined the effect of the incorporated barbiturate on the rate of respiration of the rabbit. The authors concluded that while the inclusion of a surfactant enhanced the rate of absorption of the barbiturates in some cases, it could also bind the drug, thus making it less available for the absorption process. 

Spermicides, most of which contain nonoxynol-9, are chemical surfactants that destroy sperm cell walls and offer some protection against STDs and cervical cancer. They are available as foams, creams, suppositories, jellies, and flhn. Spermicidal tablets or suppositories require 10 to 30 minutes to dissolve. Spermicides can cause local irritation in both men and women. Additional spermicide must be used each time intercourse is repeated. 

NB By extrapolation of apparent values to 0% 7-(2-hydroxypropyl)-theophylline that was used as a complexing agent to increase solubility. TRIS was used as a pKg reference (pKa = 8.18 at 20 C). See also Ritschel, who cited Fincher JH, Entrekin DN, Hartman CW, Surfactant-Base-Barbiturate Suppositories I Rectal absorption in rabbits, J. Pharm. Sci., 55,23-28 (1966). Fincher in turn cited values from Shanker LS, Absorption of drugs from the rat colon, JPET, 126,283-290 (1959) for 4 cpds 5-allyl-5-isobutylbarbituric acid (7.86) 5-butyl-5-ethylbarbituric acid (8.10) 5-efhyl-5-(l-mefiiylbutyl)barbituric acid (8.17) and 5-allyl-5-isopropylbarbituric acid (7.54). 

Uses Binder, emulsifier, surfactant, dispersant, emollient for cosmetics, pharmaceuticals, creams/lotions chemicals softener in rubber compds., food pkg., suppositories, ointments deleafing inhibitor (aerosol metallic paints) detergent intermediate for personal care, household and industrial applies. soap/shampoo ingred. mfg. of esters, lubricants, cosmetics, soaps, creams, textile and plastic auxs., plasticizers... 

Definition Polymer of ethylene oxide Formula H(OCH2CH2)nOH, avg. n = 60 Properties Vise. 67-93 cSt nonionic Toxicology TSCA listed Uses Humectant in cosmetics surfactant for suppository bases humectant, consistency agent, bulking agent in pharmaceuticals in food-pkg. adhesives... 

Behenamide DEA opacifier, suppositories Propylene glycol distearate opacifier, surfactant systems Methyl hydroxystearate opacifier, textile finishes Magnesium aluminum silicate opacifier, textiles... 

Dodoxynol-7 Dodoxynol-10 Nonoxynol-19 PEG-12 ditallate surfactant, specialties Sodium trideceth-7 carboxyiate surfactant, specialty salts Decyl diphenyloxide disulfonic acid surfactant, spice air fresheners Sodium Cl4-16 olefin sulfonate surfactant, spray cleaners a-Sulfo methyl laurate surfactant, steam cleaners Sodium capryloamphopropionate surfactant, steam cleaning Disodium capryloamphodiacetate surfactant, stool softeners Dioctyl calcium sulfosuccinate surfactant, styrene Ammonium nonoxynol-4 sulfate surfactant, styrene-acrylic Ammonium laureth sulfate surfactant, substantive foaming hair care Sodium/TEA-lauroyl hydrolyzed keratin surfactant, substantive foaming nail care Sodium/TEA-lauroyl hydrolyzed keratin surfactant, substantive foaming skin care Sodium/TEA-lauroyl hydrolyzed keratin surfactant, substantive hair conditioners Soyamidopropyl dimethylamine surfactant, suppository bases PEG-60... 

Polysorbates and sorbitan esters are used in pharmaceutical emulsions or dispersions containing vitamins or hormones. Lipophilic surfactants such as monoglycerides, propylene glycol ester or sorbitan esters are used as suppository bases. Monoglycerides and other lipophilic surfactants are typical compounds in cosmetic water/oil or oil/water creams, lotions and gels. Hydrophilic surfactants are used to solubilize perfume oils in various cosmetic oils and lotions. 

Contemporary research focuses on the development of dosage forms with a better and faster release of the active substance and on dosage forms with a delayed or controlled release. The addition of surfactants to the suppository often enhances the rate and extent of release and even the absorption of an active substance, but there are many exceptions. For a delayed or controlled release an increased viscosity of the suppository mass appears to be relevant. Most research has not yet yielded a licensed medicine. 

Non-ionic surfactants can be added to a fatty suppository base to enhance the release of poor water-soluble active substances [5b]. The results of studies on this subject, however, vary considerably. Often the in vitro release is improved, whereas the in vivo results are disappointing [8a]. This is partly caused by the formation of micelles in the rectal fluid and partly by the influence of the surfactant... 

If an active substance is practically insoluble in water (and therefore in the rectal fluid), the suppository will be ineffective. Certain excipients may increase the water solubility and, as a result, the absorption. A surfactant can be added... 

Wetting of strongly hydrophobic active substances can be so difficult that the solid particles will not get dispersed properly and float on the water. Polysorbate 80 (0.1-0.15 %) can be added to the water to prevent this. Alternatively the solid active substance can be triturated with povidone or colloidal anhydrous silica, see Sect. 29.3. Addition of a surfactant such as polysorbate should be considered carefully, because unless in small amounts it may adversely affect the absorption comparable with the addition of surfactants to suppositories (see Sect. 11.3.2). 

Rectal solutions have water or oil as a vehicle. If necessary to enhance the solubility of poorly soluble active substances, aqueous rectal solutirms may contain cosolvents, such as ethanol and propylene glycol. However, cosolvents and surfactants should only be used in limited amounts because of the potential irritation and the defecation reflex they may cause. For the rectal absorption of active substances from enemas the same mechanisms as for suppositories apply. A major advantage of a rectal solution over a suppository may be the fact that the active substance is already in a dissolved state which may increase the absorption rate. Increasing the volume of a rectal solution to dissolve a poorly water-soluble active substance will enhance the dissolution rate and thereby increase the absorption rate. Because of the higher volume more active substance will be dissolved and the membrane surface over which absorption occurs, is increased as well. 

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