Compendium of the most significant studies with reference to properties, intake, effects.

Guo Q, Bellissimo N, Rousseau D. Effect of Emulsifier Concentration and Physical State on the In Vitro Digestion Behavior of Oil-in-Water Emulsions. J Agric Food Chem. 2018 Jul 18;66(28):7496-7503. doi: 10.1021/acs.jafc.8b02231.

Abstract. The influence of emulsifier physical state and concentration on the in vitro digestion of oil-in-water (O/W) emulsions was investigated. Two citrated monoacylglycerols, glyceryl stearate citrate (GSC, bulk mp of 55-65 °C) and glyceryl oleate citrate (GOC, bulk mp of 0-10 °C), were used at 0.5 or 5 wt % of the emulsions to generate 20 wt % soybean oil O/W emulsions. Oil droplet lipolysis was slower in emulsions with 0.5 wt % emulsifier versus in those with 5 wt % emulsifier, resulting from the reduced surface-to-volume ratio in emulsions at 0.5 wt % emulsifier and the increased concentration of hydrolyzable groups at 5 wt % emulsifier. When excluding gastric digestion, all emulsions were similarly digested, confirming that emulsion intestinal digestion was highly dependent on gastric preprocessing. Finally, at a given emulsifier concentration, GSC-based emulsions with an interfacial crystalline shell experienced a decreased rate of intestinal lipid digestion compared with their GOC-based counterparts, confirming that emulsifier physical state played a role in lipid digestion.

Surianarayanan, R., & Bhaskar, J. P. (2020). Herbal cosmeceuticals. In Plant Metabolites: Methods, Applications and Prospects (pp. 217-238). Springer, Singapore.

Abstract. Herbal cosmeceutical is a rapidly growing category in the field of cosmetics and personal care products. The safety perception is the major contributing factor for the growth of this category. Therefore, the design of these products requires introspection from seed to shelf stage of the product. From good agricultural practices, through selection of ingredients for the base formulation, herbal research to eco-friendly packaging are the aspects that need to be considered to design herbal cosmeceutical products that are safe to environment and safer to consumers. This chapter talks about ways of making a cosmeceutical formulation base green, current herbal knowledge and future research perspective, regulatory considerations and industry approach to herbal products in terms of product claims.

Cefali, L. C., Ataide, J. A., Fernandes, A. R., Sousa, I. M. D. O., Gonçalves, F. C. D. S., Eberlin, S., ... & Gava Mazzola, P. (2019). Flavonoid-enriched plant-extract-loaded emulsion: a novel phytocosmetic sunscreen formulation with antioxidant properties. Antioxidants, 8(10), 443.

Abstract. The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 °C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 ± 0.39 μg/mL and 30.39 ± 0.39 μg/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 ± 1.92 μg/mL) by tape stripping and retention test (114.68 ± 8.70 μg/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.

Amended final report on the safety assessment of glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dierucate, glyceryl dihydroxystearate, glyceryl diisopalmitate, glyceryl diisostearate, glyceryl dilinoleate, glyceryl dimyristate, glyceryl dioleate, glyceryl diricinoleate, glyceryl dipalmitate, glyceryl dipalmitoleate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate, and glyceryl stearate succinate. Int J Toxicol. 2007;26 Suppl 3:1-30. doi: 10.1080/10915810701663143.

Abstract. Glyceryl Dilaurate, Glyceryl Diarachidate, Glyceryl Dibehenate, Glyceryl Dierucate, Glyceryl Dihydroxystearate, Glyceryl Diisopalmitate, Glyceryl Diisostearate, Glyceryl Dilinoleate, Glyceryl Dimyristate, Glyceryl Dioleate, Glyceryl Diricinoleate, Glyceryl Dipalmitate, Glyceryl Dipalmitoleate, Glyceryl Distearate, Glyceryl Palmitate Lactate, Glyceryl Stearate Citrate, Glyceryl Stearate Lactate, and Glyceryl Stearate Succinate are diacylglycerols (also known as diglycerides or glyceryl diesters) that function as skin conditioning agents - emollients in cosmetics. Only Glyceryl Dilaurate (up to 5%), Glyceryl Diisostearate (up to 43%), Glyceryl Dioleate (up to 2%), Glyceryl Distearate (up to 7%), and Glyceryl Stearate Lactate (up to 5%) are reported to be in current use. Production proceeds from fully refined vegetable oils, which are further processed using hydrogenation and fractionation techniques, and the end products are produced by reacting selected mixtures of the partly hydrogenated, partly fractionated oils and fats with vegetable-derived glycerine to yield partial glycerides. In the final stage of the production process, the products are purified by deodorization, which effectively removes pesticide residues and lower boiling residues such as residues of halogenated solvents and aromatic solvents. Diglycerides have been approved by the Food and Drug Administration (FDA) for use as indirect food additives. Nominally, these ingredients are 1,3-diglycerides, but are easily isomerized to the 1,2-diglycerides form. The 1,3-diglyceride isomer is not a significant toxicant in acute, short-term, subchronic, or chronic animal tests. Glyceryl Dilaurate was a mild primary irritant in albino rabbits, but not a skin sensitizer in guinea pig maximization tests. Diacylglycerol Oil was not genotoxic in the Ames test, in mammalian Chinese hamster lung cells, or in a rodent bone marrow micronucleus assay. An eye shadow containing 1.5% Glyceryl Dilaurate did not induce skin irritation in a single insult patch test, but mild skin irritation reactions to a foundation containing the same concentration were observed. A trade mixture containing an unspecified concentration of Glyceryl Dibehenate did not induce irritation or significant cutaneous intolerance in a 48-h occlusive patch test. In maximization tests, neither an eye shadow nor a foundation containing 1.5% Glyceryl Dilaurate was a skin sensitizer. Sensitization was not induced in subjects patch tested with 50% w/w Glyceryl Dioleate in a repeated insult, occlusive patch test. Glyceryl Palmitate Lactate (50% w/v) did not induce skin irritation or sensitization in subjects patch tested in a repeat-insult patch test. Phototoxicity or photoallergenicity was not induced in healthy volunteers tested with a lipstick containing 1.0% Glyceryl Rosinate. Two diacylglycerols, 1-oleoyl-2-acetoyl-sn-glycerol and 1,2-dipalmitoyl-sn-glycerol, did not alter cell proliferation (as determined by DNA synthesis) in normal human dermal fibroblasts in vitro at doses up to 10 microg/ml. In the absence of initiation, Glyceryl Distearate induced a moderate hyperplastic response in randomly bred mice of a tumor-resistant strain, and with 9,10-dimethyl-1,2-benzanthracene (DMBA) initiation, an increase in the total cell count was observed. In a glyceryl monoester study, a single application of DMBA to the skin followed by 5% Glyceryl Stearate twice weekly produced no tumors, but slight epidermal hyperplasia at the site of application. Glyceryl Dioleate induced transformation in 3-methylcholanthrene-initiated BALB/3T3 A31-1-1 cloned cells in vitro. A tumor-promoting dosing regimen that consisted of multiple applications of 10 mumol of a 1,2-diacylglycerol (sn-1,2-didecanoylglycerol) to female mice twice daily for 1 week caused more than a 60% decrease in protein kinase C (PKC) activity and marked epidermal hyperplasia. Applications of 10 micromol sn-1,2-didecanoylglycerol twice weekly for 1 week caused a decrease in cytosolic PKC activity, an increase in particulate PKC activity, and no epidermal hyperplasia. In studies of the tumor-promoting activity of 1,2-diacylglycerols, dose and the exposure regimen by which the dose is delivered play a role in tumor promotion. The 1,2-diacylglycerol-induced activation of PKC may also relate to the saturation of the fatty acid in the 1 or 2 position; 1,2-Diacylglycerols with two saturated fatty acids are less effective. Also, the activity of 1,2-diacylglycerols may be reduced when the fatty acid moiety in the structure is a long-chain fatty acid. A histological evaluation was performed on human skin from female volunteers (18 to 56 years old) who had applied a prototype lotion or placebo formulation, both containing 0.5% Glyceryl Dilaurate, consecutively for 16 weeks or 21 weeks. Skin irritation was not observed in any of the subjects tested. Biopsies (2 mm) taken from both legs of five subjects indicated no recognizable abnormalities of the skin; the epidermis was normal in thickness, and there was no evidence of scaling, inflammation, or neoplasms in any of the tissues that were evaluated. The Cosmetic Ingredient Review (CIR) Expert Panel considered that the available safety test data indicate that diglycerides in the 1,3-diester form do not present any significant acute toxicity risk, nor are these ingredients irritating, sensitizing, or photosensitizing. Whereas no data are available regarding reproductive or developmental toxicity, there is no reason to suspect any such toxicity because the dermal absorption of these chemicals is negligible. The Panel noted that these nominally 1,3-diglycerides contain 1,2-diglycerides, raising the concern that 1,2-diglycerides could potentially induce hyperplasia. Data regarding the induction of PKC and the tumor promotion potential of 1,2-diacylglycerols increased the level of concern. Most of the diglycerides considered in this safety assessment, however, have fatty acid chains longer than 14 carbons and none have mixed saturated/unsaturated fatty acid moieties. The Panel considered it particularly important that a 21-week use study of a prototype lotion containing 0.5% Glyceryl Dilaurate (a 14-carbon chain fatty acid) indicated no evidence of scaling, inflammation, or neoplasms in biopsy specimens. Also, DNA synthesis assays on Glyceryl Dilaurate and Glyceryl Distearate indicated that neither chemical altered cell proliferation (as determined by DNA synthesis) in normal human dermal fibroblasts in vitro at doses up to 10 microg/ml. The Panel understands that use testing is a common practice in industry and, if histopathology data are collected, the Panel believes that such an approach can demonstrate an absence of epidermal hyperplasia. Because the concentration of these ingredients can vary (up to 43% for Glyceryl Diisostearate in lipstick), the frequency of application can be several times daily, and the proportion of diglycerides that are inactive 1,3 isomers versus potentially biologically active 1,2 isomers is unknown, the Panel believes that each use should be examined to ensure the absence of epidermal hyperplasia during product development and testing. In the absence of inhalation toxicity data on the Glyceryl Diesters in this safety assessment, the Panel determined that these ingredients can be used safely in aerosolized products because they are not respirable. The Panel recognizes that certain ingredients in this group are reportedly used in a given product category, but the concentration of use is not available. For other ingredients in this group, information regarding use concentration for specific product categories is provided, but the number of such products is not known. In still other cases, an ingredient is not in current use, but may be used in the future. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used and at what concentration indicate a pattern of use. Within this overall pattern of use, the CIR Expert Panel considers all ingredients in this group to be safe.

Zahir-Jouzdani F, Lupo N, Hermann M, Prüfert F, Atyabi F, Bernkop Schnürch A. Glyceryl ester surfactants: Promising excipients to enhance the cell permeating properties of SEDDS. Eur J Pharm Biopharm. 2018 Aug;129:154-161. doi: 10.1016/j.ejpb.2018.05.032. 

Abstract. Aim: The aim of the study is the evaluation of the impact of glyceryl ester surfactants on cell permeating properties of SEDDS (self-emulsifying drug delivery systems)....Conclusions: Glyceryl ester surfactants and in particular polyglyceryl-3-stearate might be a promising excipient for the formulation of SEDDS exhibiting enhanced cellular uptake and permeation enhancing properties. Copyright © 2018 Elsevier B.V.

Glyceryl Stearate Citrate is a chemical compound, fatty acid monoglyceride, formed from glycerine, stearic acid (generally from soybean, rapeseed, canola and maize oils) and citric acid, glycerol stearate ester of citric acid and stearic acid. It is a monoglyceride of fatty acids of vegetable origin but esterified and therefore not 100 per cent natural. Anionic.

Glyceryl Stearate Citrate is an emulsifier commonly used in cosmetics and personal care products. It is derived from plant-based sources, such as vegetable oils, and is used to help blend water and oil-based ingredients in formulations. Known for its ability to improve the texture and stability of cosmetic products, Glyceryl Stearate Citrate also functions as a skin-conditioning agent, making it a versatile ingredient in skincare and haircare products.

Chemical Composition and Structure

Glyceryl Stearate Citrate is formed from the esterification of glycerin, stearic acid, and citric acid. The combination of these components results in an ingredient that serves as a mild emulsifier and stabilizer. Glycerin, known for its hydrating properties, is combined with stearic acid (a fatty acid) and citric acid to create a compound that helps emulsify and soften the skin.

Physical Properties

It is usually a white to off-white, waxy solid. It is oil-soluble but can disperse well in water when used in emulsions, making it ideal for use in lotions, creams, and other emulsified products. Its ability to blend and stabilize oil-in-water emulsions ensures a smooth, uniform texture in cosmetic formulations.

Production Process

The production of Glyceryl Stearate Citrate involves the esterification of glycerin (derived from vegetable oils) with stearic acid and citric acid. The process results in a stable emulsifying agent that can be used in various cosmetic formulations to help mix oil and water-based components, creating a smooth and homogenous product.

It appears as a white powder suitable for the production of oil/water emulsions, insoluble and dispersible in hot water, soluble in oil at high temperatures. Easily hydrolysed under conditions of strong alkalis or strong acids.

What it is used for and where

Cosmetics

• Skin conditioning agent - Emollient. Emollients have the characteristic of enhancing the skin barrier through a source of exogenous lipids that adhere to the skin, improving barrier properties by filling gaps in intercorneocyte clusters to improve hydration while protecting against inflammation. In practice, they have the ability to create a barrier that prevents transepidermal water loss.  Emollients are described as degreasing or refreshing additives that improve the lipid content of the upper layers of the skin by preventing degreasing and drying of the skin. The problem with emollients is that many have a strong lipophilic character and are identified as occlusive ingredients; they are oily and fatty materials that remain on the skin surface and reduce transepidermal water loss. In cosmetics, emollients and moisturisers are often considered synonymous with humectants and occlusives.
• Surfactant - Emulsifying agent. Emulsions are thermodynamically unstable and are used to soothe or soften the skin and emulsify, so they need a specific, stabilising ingredient. This ingredient forms a film, lowers the surface tension and makes two immiscible liquids miscible. A very important factor affecting the stability of the emulsion is the amount of the emulsifying agent. Emulsifiers have the property of reducing the oil/water or water/oil interfacial tension, improving the stability of the emulsion and also directly influencing the stability, sensory properties and surface tension of sunscreens by modulating the filmometric performance.
• Skin conditioning agent. It is the mainstay of topical skin treatment as it has the function of restoring, increasing or improving skin tolerance to external factors, including melanocyte tolerance. The most important function of the conditioning agent is to prevent skin dehydration, but the subject is rather complex and involves emollients and humectants that can be added in the formulation.

Used as an oil/water emulsifier with medium/low viscosity even for PEG-free formulations and with an optimal oil-phase concentration of 25-35%. Possesses high hydrophilic-lipophilic balance (HLB) 

Acts as a non-ethoxylated hydrophilic emulsifier and as a co-emulsifier for PEG-free formulations. Anionic surfactant, softening agent for softening skin, skin conditioner and fragrance (1), also for sensitive skin. It has the function of helping skin and hair retain moisture and tends to form a gel system in the aqueous phase of the emulsion. Emulsifiers have the property of reducing interfacial tension and also directly influence the stability, sensory properties and surface tension of sunscreens by modulating their filmometric performance. 

Dosage: Glyceryl Stearate Citrate is included in cosmetic formulations in percentages between 0.25%, 2% (improves viscosity of rinse-off products that have difficulty thickening with sodium chloride) and 4%. When added to hot water it is not soluble, but must be stirred to obtain a cloudy liquid ready for emulsification.

Food

Emulsifier, fragrance.

Other uses

Double emulsions are promising delivery vehicles for the protective and programmed release of bioactive compounds. In the digestive phase Glyceryl Stearate Citrate forms a kind of crystalline shell and has been shown to decrease the rate of intestinal lipid digestion in the oil/water emulsion (2).

Safety. The purity level of commercial monoglyceric monoester is about 90 per cent, and impurities include fatty acids, monoglyceric diesters, mono-, di- and tri-glycerides.

Safety in Use
Glyceryl Stearate Citrate is considered safe for use in cosmetic products. It is non-irritating, non-toxic, and generally well-tolerated by the skin, making it suitable for sensitive skin types. Its plant-derived components and mild emulsifying properties make it a popular choice in natural and organic cosmetic formulations.

Allergic Reactions
Allergic reactions to Glyceryl Stearate Citrate are rare. It is a gentle ingredient, and its plant-based origins make it less likely to cause irritation. However, as with any cosmetic ingredient, individuals with sensitive skin should perform a patch test before using products that contain it.

Toxicity and Carcinogenicity
It has been thoroughly evaluated for safety and is approved for use in cosmetics and personal care products at concentrations that are considered safe for consumers.

Environmental and Safety Considerations
Glyceryl Stearate Citrate is biodegradable and does not pose significant environmental risks. It is derived from renewable, plant-based sources, making it an eco-friendly choice in cosmetic formulations.

Regulatory Status
Glyceryl Stearate Citrate is approved for use in cosmetics and personal care products by regulatory bodies such as the European Union and the Food and Drug Administration (FDA) in the United States. It is regulated to ensure safe use in a wide range of cosmetic formulations.

For more information:

Glyceryl Stearate Citrate studies

Typical commercial product characteristics Glyceryl Stearate Citrate

Appearance	White powder
pH	5.5-8.0
Boiling Point	>260°C (500°F)
Melting Point	58-64°C (136.4-147.2°F)
Acid value	0,00-20,00 mg KOH/g
HLB value/range	12
Shelf life	2 Years
Storage	dry place, protected from direct sunlight, heat
Chemical safety

Prezzo

100g    $5

• Molecular Formula   C₂₈H₅₄O₁₂    C₂₃H₄₆O₆
• Molecular Weight      582.7
• Exact Mass   582.361511
• CAS    39175-72-9    55840-13-6   86418-55-5
• UNII    WH8T92A065
• EC Number   259-855-5
• DSSTox Substance ID  DTXSID00204440
• IUPAC  3-(carboxymethyl)-3-hydroxypentanedioic acid;octadecanoic acid;propane-1,2,3-triol
• InChl=1S/C18H36O2.C7H10O7.C3H8O3/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20;8-4(9)1-7(14,2-5(10)11)3-6(12)13;4-1-3(6)2-5/h2-17H2,1H3,(H,19,20);14H,1-3H2,(H,8,9)(H,10,11)(H,12,13);3-6H,1-2H2
• InChl Key      HFJHNGKIVAKCIW-UHFFFAOYSA-N
• SMILES   CCCCCCCCCCCCCCCCCC(=O)O.C(C(CO)O)O.C(C(=O)O)C(CC(=O)O)(CC(=O)O)O
• ChEBI  176146 

Synonyms:

• 3-(carboxymethyl)-3-hydroxypentanedioic acid;octadecanoic acid;propane-1,2,3-triol
• Stearyl monoglyceridyl citrate
• 1,2,3-Propanetricarboxylic acid, 2-hydroxy-, ester with 1,2,3-propanetriol monooctadecanoate
• Monostearin citrate
• Glycerol stearate citrate

References_____________________________________________________________________

(1) Cefali, L. C., Ataide, J. A., Fernandes, A. R., Sousa, I. M. D. O., Gonçalves, F. C. D. S., Eberlin, S., ... & Gava Mazzola, P. (2019). Flavonoid-enriched plant-extract-loaded emulsion: a novel phytocosmetic sunscreen formulation with antioxidant properties. Antioxidants, 8(10), 443.

Abstract. The aim of this study was to develop a phytocosmetic sunscreen emulsion with antioxidant effect, containing a blend of flavonoid-enriched plant extracts. In vitro sun protection factor, antioxidant activity, skin irritation, photostability, cutaneous permeation, and retention of flavonoids were evaluated. Thermodynamically stable emulsions were obtained and tested for sensorial analysis after loading the blend of extracts. The selected emulsion was stable when stored at low temperatures (5 C), for which after 120 days the concentration of quercetin and rutin were above their limit of quantification, i.e., 2.8 ± 0.39 µg/mL and 30.39 ± 0.39 µg/mL, respectively. Spreadability, low rupture strength and adhesiveness were shown to be similar to a conventional topical product. Higher brittleness, pseudo-plastic, and viscoelastic behaviors were also recorded for the developed phytocosmetic sunscreen. The product presented a critical wavelength of 387.0 nm and ultraviolet rays A and B (UVA/UVB) rate of 0.78, confirming that the developed formulation shows capacity for UVA/UVB protection, protecting skin against damages caused by Ultraviolet (UV) radiation. Rutin was shown to permeate the skin barrier and was also quantified in the stratum corneum (3.27 ± 1.92 µg/mL) by tape stripping and retention test (114.68 ± 8.70 µg/mL). The developed flavonoid-enriched phytocosmetic was shown to be non-irritant to skin by an in vitro assay. Our results confirm the antioxidant activity, sun protection, and physical properties of the developed phytocosmetic for topical application.

(2) Li, W., Wang, W., Yong, C., Lan, Y., Huang, Q., & Xiao, J. (2022). Effects of the Distribution Site of Crystallizable Emulsifiers on the Gastrointestinal Digestion Behavior of Double Emulsions. Journal of Agricultural and Food Chemistry, 70(16), 5115-5125.

Abstract. Double emulsions (DEs) are promising delivery vehicles for the protective and programmed release of bioactive compounds. Herein, DEs with monoglycerides crystallized at the internal- or external interface or oil phase were fabricated. The results suggested that the crystallization site of monoglycerides exerts a significant role in retarding the structural degradation and lipid digestion of DEs by affecting the available contact area of lipase. At the initial stage of intestinal digestion, compared with noncrystalline DEs (82.1%, 3.7 min), the burst release of internal markers in the internal interface crystallized emulsions was decreased by 42.4% and the lag time of free fatty acid (FFA) release was delayed by 5.8 min in the external interface crystallized emulsions. The structural integrity and digestion kinetics of the external interface crystallized DEs were synchronized with the retention time of the interfacial crystals. Therefore, crystallizable emulsifiers exhibit unique and fine regulatory effects on the digestive properties of emulsions.