encyclopedia

Glycerol Stearate

Natural Sources:     

Starting materials used for making commercial grade Glycerol Stearate (a normal byproduct of digestion) can be obtained from animal fats and plant oils including soya bean, palm kernel and corn oil. Glycerol Stearate is generally prepared commercially from glycerine and fatty acids derived from corn or hydrogenated soya bean oil.     

Forms:     

Glycerol Monostearate; Glycerol monohydroxystearate.     

Therapeutic Uses:     

– Drug Delivery
– Eczema
– Emollient
– Emulsifier
– Moisturizer     

Overview:     

Glycerol stearate is a natural fatty compound often used as an emulsifier, emulsion stabilizer, emollient, moisturizer and viscosity builder in creams and lotions. It is also used as an opacifying and pearlizing agent in cosmetics. Glycerol stearate can be of plant origin (corn-based), animal source or synthetic and is considered to be biodegradable, practically non-toxic orally and causes no skin and minimal eye irritation. It is dispersible in water and is also soluble in oil and alcohol, making it an ideal ingredient for cosmetics. Glycerol monostearate (GMS) is also used as an ingredient in cosmetics as well as in food products. In a clinical trial with over 1,200 patients with eczema, glycerol monostearate was found to produce absolutely no adverse reactions in a test of common emulsifiers (all other emulsifiers tested did cause adverse reactions in a significant percentage of patients). It is used to keep bakery goods fresh, improve flour quality, and as an emulsifying and whopping agent for ready-to-eat products. It is also used in ice cream formulations, starch products, milk products, chewing gum, chocolates and other foods. It also serves as a softer in textiles and as an external lubricant for plastics. Another form of this chemical often used in cosmetics is glycerol monohydroxystearate, an off-white wax with physical properties similar to beeswax. It provides the functional characteristics of glycerol stearate and enhanced properties such as improved emulsion stability, bodying and thickening properties and greater dispersability of colorants and active materials. Semi-synthetic forms of glycerol stearate often use stearic acid isolated from palm oil as a starting material, another waxy fatty acid widely used in cosmetics and soap. The glycerol component of glycerol stearate can be from beef fat, petroleum, or vegetable source and is itself used as a solvent and humectant (maintains the desired moisture level).     

Chemistry:     

Glycerol stearate is a fatty compound (C17H35COO)3C3H5). The formula for the hydrocarbon radical (R­) in the fat glycerol stearate is C17H35. Glycerol stearate has a melting point of 58°C / 136°F, an acid value of 15, and an iodine value of 1.5. Fats are technically described as esters of fatty acids and glycerol (soaps are metallic salts of fatty acids). The reaction of glycerol stearate with sodium hydroxide to produce the soap sodium stearate has the following chemical equation: C17H35COO)3C3H5 + 3 NaOH -> C3H5(OH)3 + 3 C17H35COONa. Glycerol monostearate has an acid value of 2% and a maximum iodine value of 5. It is classified as an anionic modified emulsifier recommended for use in oil or water emulsions that are in the pH range of 5 – 9. It has a melting point of between 54Ί – 60ΊC, monoglyceride content between 42-45%, maximum free glycerine content of 10% and water content of 1.5%. Mono- and diglycerides of fatty acids (glyceryl monostearate, glyceryl distearate) are a normal part of digestion, prepared commercially from glycerine and fatty acids. These are normally obtained from hydrogenated soya bean oil so may be GMP grade.     

Suggested Amount:     

Glycerol stearate is recommended for use in creams and other cosmetics at the level of approximately 0.5-2% w/w.     

Drug Interactions:     

None known.     

Contraindications:     

None known.     

Side Effects:     

None known.     

References:     

D'Antona P, Parker WO, Zanirato MC, Esposito E, Nastruzzi C. 2000. Rheologic and NMR characterization of monoglyceride-based formulations. J Biomed Mater Res 2000 Oct; 52(1): 40-52.
 
Hannuksela M, Kousa M, Pirila V. 1976. Contact sensitivity to emulsifiers. Contact Dermatitis 1976 Aug; 2(4): 201-4.
 
Lewis L, Boni R, Adeyeye CM. 1998. Effect of emulsifier blend on the characteristics of sustained release diclofenac microspheres. J Microencapsul 1998 May-Jun; 15(3): 283-98.
 
Pasich J, Bether W, Malaga M. 1981. [The dynamics of the drug release from ointment bases. Part 5: The effects of tensides on the liberation of atropine from eye ointments (author's transl)] Pharmazie 1981 Apr; 36(4): 267-9. [Article in German]

Additional Information:     

Glycerol Stearate Research Abstracts:

Hannuksela M, Kousa M, Pirila V. 1976. Contact sensitivity to emulsifiers. Contact Dermatitis 1976 Aug; 2(4): 201-4.
 
Common emulsifiers were tested in over 1,200 patients with eczema. Triethanolamine stearate tested at 5% in petrolatum caused irritant reactions in 9.5% of the patients. On the other hand, non-ionic emulsifying agents tested at 10-20% produced irritation in only a few cases. Allergic reactions were found in 2.1% of those tested. Lanette, sorbitan sesquioleate, the Spans, polyoxyethylene oxypropylene stearate, polyoxyethylene sorbitol lanolin derivative, and triethanolamine stearate each elicited allergic reactions in 0.3-0.7% of the cases. The Tweens caused an allergy in only two cases, but glycerol monostearate caused no reaction at all. Five out of six patients sensitive to sorbitan sesquioleate reacted positively to the Spans as well. The patients allergic to one or more emulsifiers were also sensitive to several other substances included in our routine test series with the exception of four patients who reacted only to the emulsifying agents.

Pasich J, Bether W, Malaga M. 1981. [The dynamics of the drug release from ointment bases. Part 5: The effects of tensides on the liberation of atropine from eye ointments (author's transl)] Pharmazie 1981 Apr; 36(4): 267-9. [Article in German]
 
The liberation of atropine sulphate from 12 eye ointments added with lipophil emulsifiers (cholesterol and glycerol monostearate) and propylene glycol was determined in vitro in the apparatus of Olszewski and Kubis, using the reaction of atropine with bromothymol blue for spectrometric estimation. The best release was observed with vaseline added with propylene glycol. In contrast, glycerol monostearate and cholesterol produced no considerable increase in liberation. Glycerol monostearate exerted the greatest effect on the liberation of atropine sulphate from the base described in the Polish Pharmacopoeia IV. Glycerol monostearate was the most suited emulsifier for a paraffin-lanolin-water base. The maximum of release is delayed by the addition of the emulsifier to the ointment base.

Lewis L, Boni R, Adeyeye CM. 1998. Effect of emulsifier blend on the characteristics of sustained release diclofenac microspheres. J Microencapsul 1998 May-Jun; 15(3): 283-98.
 
Graduate School of Pharmaceutical Sciences, Duquesne University, Pittsburgh, PA 15282, USA.
 
This investigation involved the evaluation of the emulsifier blend effect on the development of sustained release diclofenac microspheres intended for use in a suspension formulation. The microspheres were prepared using the hydrophobic congealable disperse phase method. The emulsifier blend consisted of glycerol, monostearate (GMS), a hydrophobic emulsifier with HLB = 3.8, and Tween 80, a hydrophilic emulsifier with a HLB value of 15. The effect of this blend on the encapsulation efficiency, size distribution and drug release from the microspheres was studied. A critical amount of GMS (> 0.2 g) was found to be necessary for good encapsulation efficiency. X-ray diffractograms revealed that the drug retains its crystalline state within the microspheres, indicating that the drug is present as a dispersion within the wax matrix. Increasing amounts of Tween 80 caused an increase in the drug release while increased amounts of GMS retarded the release. The hydrophilic emulsifier and the emulsifier blend influenced the size distribution of the formed microspheres. With an increase in the amount of hydrophilic emulsifier, there was an initial increase in the percent of desired size fraction (137.5 microns) of microspheres followed by a decrease. Microspheres with a larger size released the drug slowly compared to smaller size microspheres, while increase in drug load increased the rate of drug release. The release pattern fitted the Higuchi dissolution kinetics for spherical matrices. Different impeller blade designs formed microspheres that exhibited different release rates. The microspheres (mean size 137.5 microns), had a release profile that made them suitable to be formulated as a sustained release suspension.
 
D'Antona P, Parker WO, Zanirato MC, Esposito E, Nastruzzi C. 2000. Rheologic and NMR characterization of monoglyceride-based formulations. J Biomed Mater Res 2000 Oct; 52(1): 40-52.
 
Eni Tecnologie, San Donato Milanese, Milano, Italy.
 
This paper describes the production and characterization of semi-solid formulations based on monoglycerides from canola oil and water as drug-delivery systems. In order to obtain new formulations with different characteristics in terms of viscosity, bioadhesiveness, and solubilization capacity, a third component was added to the monoglyceride-water system. Nine excipients were tested, namely soy oil, isopropylmyristate, isopropylpalmitate, tripalmitin, tristearin, glyceryl monostearate, glycerol, propylene glycol, and ethanol. In particular, the effect of each excipient on the viscosity and stability of the formulation was investigated. It was found that ethanol dramatically influenced the viscosity of the monoglyceride-water system, resulting in the formation of stable forms. In addition, ethanol suitably could be used for the solubilization of water-insoluble lipophilic drugs. This promising ternary system was characterized by microscopic, NMR spectroscopic, and rheologic techniques. (1)H and (13)C NMR studies were made of Myverol to verify the molecular structure and isomer distributions of this commercial monoacylglycerol mixture. The microstructure of an isotropic solution consisting of Myverol [1.8% (w/w)], ethanol (42.9%), and water (55.3%) was studied by the multi-component self-diffusion NMR method. From the self-diffusion coefficient (D) of the monoglycerides (8.8 x 10-11 m(2)/s), an “apparent spherical hydrodynamic radius” of ca. 2.48 nm was calculated for the micellar aggregate. A nearly spherical shape is consistent with these values since the extended hydrocarbon chain of the longest monoglyceride (17 carbons) is ca. 2.2 nm long. The D's of water and ethanol reveal they do not associate (no attractive nonbonding interactions) appreciably with the fatty acid micelles. Copyright 2000 John Wiley & Sons, Inc.

Int J Toxicol 2001;20 Suppl 2:65-77
 
Final report on the safety assessment of Peanut (Arachis hypogaea) Oil, Hydrogenated Peanut Oil, Peanut Acid, Peanut Glycerides, and Peanut (Arachis hypogaea) Flour.
 
Peanut (Arachis Hypogaea) Oil is the refined fixed oil obtained from the seed kernels of Arachis hypogaea. Hydrogenated Peanut Oil, Peanut Acid, and Peanut Glycerides are all derived from Peanut Oil. Peanut Flour is a powder obtained by the grinding of peanuts. The oils and glycerides function in cosmetic formulations as skin-conditioning agents. The acid functions as a surfactant-cleansing agent, and the flour functions as an abrasive, bulking agent and/or viscosity-increasing agent. In 1998, only Peanut Oil and Hydrogenated Peanut Oil were reported in use. When applied to the skin, Peanut Oil can enhance the absorption of other compounds. Hepatic changes were noted at microscopic examination of rats fed diets containing 15% edible Peanut Oil for 28 days, although no control group was maintained and the findings were also noted in rats fed fresh corn oil. United States Pharmacopeia (USP)-grade Peanut Oil was considered relatively nonirritating when injected into guinea pigs and monkeys. Technical-grade Peanut Oil was moderately irritating to rabbits and guinea pigs and mildly irritating to rats following dermal exposure. This same oil produced reactions in < or = 10% of 50 human males. Peanut Oil was not an ocular irritant in rabbits. Peanut Oil, either "laboratory expressed" or extracted using a food-grade solvent, was not carcinogenic to mice. Peanut Oil exerted anticarcinogenic activity when tested against known carcinogens. Peanuts are the food most likely to produce allergic and anaphylactic reactions. The major allergen is a protein that does not partition into Peanut Oil, Hydrogenated Peanut Oil, Peanut Acid, and Peanut Glycerides. Aflatoxins can be produced in stored agricultural crops such as peanuts, but do not partition into the oils, acids, or glycerides. Manufacturers were cautioned to make certain that the oils, acids, and glycerides are free of aflatoxins and protein. Formulators were cautioned that the oils, acids, or glycerides may enhance penetration and can affect the use of other ingredients whose safety assessment was based on their lack of absorption. The available studies on Peanut Oil supported the conclusion that Peanut Oil, Hydrogenated Peanut Oil, Peanut Acid, and Peanut Glycerides are safe for use in cosmetic formulations. Peanut (Arachis Hypogaea) Flour, however, is sufficiently different from the above ingredients such that its safety can not be supported by studies using the oil. The additional data needed for Peanut (Arachis Hypogaea) Flour are (1) concentration of use; (2) chemical specifications (i.e., aflatoxin and protein levels); (3) method of preparation; and (4) contact urticaria and dermal sensitization at concentration of use. Although data on aflatoxin levels are sought, it is expected that concentrations of aflatoxin should comply with U.S. government stipulations. Absent the additional data, it was concluded that the available data are insufficient to support the safety of Peanut (Arachis Hypogaea) Flour for use in cosmetic products.
 

Int J Toxicol 2001;20 Suppl 4:61-94
 
Final report on the safety assessment of trilaurin, triarachidin, tribehenin, tricaprin, tricaprylin, trierucin, triheptanoin, triheptylundecanoin, triisononanoin, triisopalmitin, triisostearin, trilinolein, trimyristin, trioctanoin, triolein, tripalmitin, tripalmitolein, triricinolein, tristearin, triundecanoin, glyceryl triacetyl hydroxystearate, glyceryl triacetyl ricinoleate, and gl.
 
Johnson W Jr; Cosmetic Ingredient Review Expert Panel.
 
Cosmetic Ingredient Review, Washington, DC 20036, USA.
 
Triesters of glycerin and aliphatic acids, known generically as glyceryl triesters and specifically as Trilaurin, etc., are used in cosmetic products as occlusive skin-conditioning agents and/or nonaqueous viscosity-increasing agents. Hundreds of glyceryl triesters are used in a wide variety of cosmetic products at concentrations ranging from a few tenths of a percent to 46%. Glyceryl triesters are also known as triglycerides; ingested triglycerides are metabolized to monoglycerides, free fatty acids, and glycerol, all of which are absorbed in the intestinal mucosa and undergo further metabolism. Dermal absorption of Triolein in mice was nil; the oil remained at the application site. Only slight absorption was seen in guinea pig skin. Tricaprylin and other glyceryl triesters have been shown to increase the skin penetration of drugs. Little or no acute, subchronic, or chronic oral toxicity was seen in animal studies unless levels approached a significant percentage of caloric intake. Subcutaneous injections of Tricaprylin in rats over a period of 5 weeks caused a granulomatous reaction characterized by oil deposits surrounded by macrophages. Dermal application was not associated with significant irritation in rabbit skin. Ocular exposures were, at most, mildly irritating to rabbit eyes. No evidence of sensitization or photosensitization was seen in a guinea pig maximization test. Most of the genotoxicity test systems were negative. Tricaprylin, Trioctanoin, and Triolein have historically been used as vehicles in carcinogenicity testing of other chemicals. In one study, subcutaneous injection of Tricaprylin in newborn mice produced more tumors in lymphoid tissue than were seen in untreated animals, whereas neither subcutaneous or intraperitoneal injection in 4- to 6-week-old female mice produced any tumors in another study. Trioctanoin injected subcutaneously in hamsters produced no tumors. Trioctanoin injected intraperitoneally in pregnant rats was associated with an increase in mammary tumors in the offspring compared to that seen in offspring of untreated animals, but similar studies in pregnant hamsters and rabbits showed no tumors in the offspring. One study of Triolein injected subcutaneously in rats showed no tumors at the injection site. As part of an effort to evaluate vehicles used in carcinogenicity studies, the National Toxicology Program conducted a 2-year carcinogenicity study in rats given Tricaprylin by gavage. This treatment was associated with a statistically significant dose-related increase in pancreatic acinar cell hyperplasia and adenoma, but there were no acinar carcinomas, the incidence of mononuclear leukemia was less, and nephropathy findings were reduced, all compared to corn oil controls. Overall, the study concluded that Tricaprylin did not offer significant advantages over corn oil as vehicles in carcinogenicity studies. Trilaurin was found to inhibit the formation of neoplasms initiated by dimethylbenzanthracene (DMBA) and promoted by croton oil. Tricaprylin was not teratogenic in mice or rats, but some reproductive effects were seen in rabbits. A low level of fetal eye abnormalities and a small percentage of abnormal sperm were reported in mice injected with Trioctanoin as a vehicle control. Clinical tests of Trilaurin at 36.3% in a commercial product applied to the skin produced no irritation reactions. Trilaurin, Tristearin, and Tribehenin at 40%, 1.68%, and 0.38%, respectively, in commercial products were also negative in repeated-insult patch tests. Tristearin at 0.32% in a commercial product induced transient, mild to moderate, ocular irritation after instillation into the eyes of human subjects. Based on the enhancement of penetration of other chemicals by skin treatment with glyceryl triesters, it is recommended that care be exercised in using them in cosmetic products. On the basis of the available data, the following 23 glyceryl triesters are considered safe as used in cosmetics: Trilaurin, Triarachidin, Tribehenin, Tricaprin, Tricaprylin, Trierucin, Triheptanoin, Triheptylundecanoin, Triisononanoin, Triisopalmitin, Triisostearin, Trilinolein, Trimyristin, Trioctanoin, Triolein, Tripalmitin, Tripalmitolein, Triricinolein, Tristearin, Triundecanoin, Glyceryl Triacetyl Hydroxystearate, Glyceryl Triacetyl Ricinoleate, and Glyceryl Stearate Diacetate. Some of these are not currently in use, but would be considered safe if used at concentrations similar to those glyceryl triesters that are in use as cosmetic ingredients.
 

Int J Toxicol 2001;20 Suppl 2:57-64

Final report on the safety assessment of Lard Glyceride, Hydrogenated Lard Glyceride, Lard Glycerides, Hydrogenated Lard Glycerides, Lard and Hydrogenated Lard.
 
Lard obtained from the rendering of fatty porcine tissue is used in cosmetic products, as are several of its derivatives. These derivatives include Lard Glycerides (mono-, di-, and triglycerides derived from Lard), Lard Glyceride (the monoglycerides only), Hydrogenated Lard Glycerides, Hydrogenated Lard Glyceride, and Hydrogenated Lard. The latter three are produced by controlled hydrogenation of the described precursor. These ingredients function as skin-conditioning agents and, with the exception of Lard, as viscosity-increasing agents in several cosmetic products. No information was available regarding the fate during processing of impurities such as pesticides or heavy metals that may be found in animal tissue. Lard itself is established by the Food and Drug Administration (FDA) as a GRAS (generally recognized as safe) substance. Animal studies report adverse effects expected with the feeding of high fat diets, but other animal toxicity data were not available. Lard was not mutagenic in transgenic mice. Cell proliferation assays showed more proliferation in mice fed Lard compared to those fed plant-source fats, but another study showed no difference. Cocarcinogenic effects were observed when high-fat diets containing Lard were fed, with known carcinogens, to mice, rats, and hamsters. Consistent with the FDA GRAS determination, it was concluded that these ingredients may be used safely in cosmetic formulations. However, it was considered important to limit the presence of heavy metals and/or polychlorinated biphenyl (PCB) or other pesticide contamination. Accordingly, limits were established as follows: lead, not more than 0.1 ppm; arsenic (as As), < or =3 ppm; mercury (as Hg), < or =1 ppm; and total PCB/pesticide contamination, not more than 40 ppm, with not more than 10 ppm for any specific residue.
 

Lipids 1993 Jun;28(6):539-47
Interrelationship of stearic acid content and triacylglycerol composition of lard, beef tallow and cocoa butter in rats.
 
Monsma CC, Ney DM.
 
Department of Nutritional Sciences, University of Wisconsin, Madison 53706.
 
We investigated modes whereby stearic acid (18:0) exerts a neutral or cholesterol-lowering effect using dietary fats which provided graded levels of 18:0 and distinct triacylglycerol (TAG) profiles. Male Sprague-Dawley rats (150-175 g) were fed diets containing 0.2% cholesterol and 16% fat from corn oil, or from 1% corn oil plus 15% lard (13.2% 18:0), beef tallow (19.2% 18:0) or cocoa butter (34.7% 18:0) for 3 wk, and then killed in a fasted or fed state. Chylomicron (CM) fatty acid profiles suggested reduced absorption of 18:0 with greater 18:0 intake. CM TAG profiles indicated a reduction or loss of two TAG species compared to the TAG profiles of the stearate-rich diets: 1-palmitoyl-2-oleoyl-3-stearoyl glycerol (POS) and 1,3-distearoyl-2-oleoyl glycerol (SOS). Hepatic total cholesterol concentrations were 54-77% lower (P < 0.01) in the cocoa butter-fed than the lard-and beef tallow-fed groups. The cocoa butter group showed a significantly lower ratio of high-density lipoprotein esterified/free cholesterol than all other groups. Hepatic stearoyl-CoA and oleoyl-CoA concentrations, the substrate and product for hepatic delta 9 desaturase, were not significantly different for corn oil-fed and cocoa butter-fed groups in spite of a large difference in 18:0 intake. These data suggest that the neutral or cholesterol-lowering effect of 18:0 is not due to hepatic conversion of stearic to oleic acid, and that POS and SOS are poorly absorbed from stearate-rich dietary fats.
Am J Clin Nutr 1978 Oct;31(10 Suppl):S273-S276
 
Studies in man of partially absorbed dietary fats.
 
Hashim SA, Babayan VK.
 
A saturated long-chain triglyceride (SLCT) has been prepared by esterification with glycerol of the saturated long-chain fatty acid fraction of coconut oil, isolated by molecular distillation of the hydrolyzed oil. The resultant SLCT is comprised principally of stearate (89%) and palmitate (11%). The intestinal absorption of SLCT in man was compared with that of corn oil or a 1:1 mixture of SLCT and corn oil. Each fat or the mixture was incorporated in isocaloric amounts into a complete formula diet deriving 30% of its caloric content from fat, 55% from carbohydrate (dextrose), and 15% from protein (casein). The formula diets were administered in sequential feeding periods as the sole source of food. The results indicate that SLCT was poorly absorbed (31 to 39%) compared with virtually complete absorption of corn oil (98%). Fat absorption was improved when the dietary fat was an equal mixture of SLCT and corn oil. The poor absorption of SLCT was ascribed to its high melting point and related to impaired emulsification and micellar solubilization in the small intestine.
 

Biol Pharm Bull 1999 Apr;22(4):402-6

Effects of fatty acid glycerol esters on intestinal absorptive and secretory transport of ceftibuten.
 
Koga K, Murakami M, Kawashima S.
 
Division of Pharmaceutical Information, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
 
The effects of fatty acid glycerol esters and Tweens on the intestinal transport of ceftibuten were studied using a diffusion chamber system. The apparent permeation coefficient (P(app)) was used as an index of the mucosal permeability to ceftibuten. The P(app) markedly increased by the addition of hexaglycerol monostearate (HGMS) or hexaglycerol sesquistearate (HGSS) under an H+-gradient condition, while hexaglycerol tristearate (HGTS) and Tweens showed no effect on the absorptive ceftibuten permeability. These results are in agreement with those obtained in the previous study in the brush-border membrane vesicles. On the other hand, in the absence of an H+-gradient, the S-to-M transport of ceftibuten was proven to be significantly higher than the M-to-S one. In addition, either ATP-depletion of the mucosa or the addition of probenecid proved to enhance significantly the permeability of ceftibuten. These findings suggest the existence of an active secretory transport system for ceftibuten in the jejunal mucosa. To estimate potential effects of glycerol esters on efflux pumps as well as peptide transporters, the mucosal-to-serosal (M-to-S) and serosal-to-mucosal (S-to-M) permeability in the presence of the esters was further examined. HGMS, HGSS and HGTS markedly enhanced the M-to-S but not the S-to-M transport in the ATP-depleted jejunum without an H+-gradient, in which conditions contributions of both peptide transporter and efflux pump should be substantially small. HGMS and HGSS significantly enhanced the M-to-S ceftibuten transport in the ATP-depleted jejunum with an H+-gradient (p<0.01 vs. M-to-S transport without surfactant under the same conditions). Whereas, these glycerol esters were found hardly to affect the P(app) of the S-to-M transport. These results indicate that the enhanced intestinal transport of ceftibuten due to the glycerol esters may be based on their effects on peptide transporters but neither on efflux pumps nor on the passive permeation routes.