Polyglycerol Esters Of Fatty Acids Research Articles

Mechanically promoted lipid-based filaments via composition tuning for extrusion-based 3D-printing

Lipid excipients are favorable materials in pharmaceutical formulations owing to their natural, biodegradable, low-toxic and solubility/permeability enhancing properties. The application of these materials with advanced manufacturing platforms, particularly filament-based 3D-printing, is attractive for personalized manufacturing of thermolabile drugs. However, the filament’s weak mechanical properties limit their full potential. In this study, highly flexible filaments were extruded using PG6-C16P, a lipid-based excipient belonging to the group of polyglycerol esters of fatty acids (PGFAs), based on tuning the ratio between its major and minor composition fractions. Increasing the percentage of the minor fractions in the system was found to enhance the relevant mechanical filament properties by 50-fold, guaranteeing a flawless 3D-printability. Applying a novel liquid feeding approach further improved the mechanical filament properties at lower percentage of minor fractions, whilst circumventing the issues associated with the standard extrusion approach such as low throughput. Upon drug incorporation, the filaments retained high mechanical properties with a controlled drug release pattern. This work demonstrates PG6-C16 P as an advanced lipid-based material and a competitive printing excipient that can empower filament-based 3D-printing.

Inhibition of Tolaasin Cytotoxicity Causing Brown Blotch Disease in Cultivated Mushrooms Using Tolaasin Inhibitory Factors.

Tolaasin, a pore-forming bacterial peptide toxin secreted by Pseudomonas tolaasii, causes brown blotch disease in cultivated mushrooms by forming membrane pores and collapsing the membrane structures. Tolaasin is a lipodepsipeptide, MW 1985, and pore formation by tolaasin molecules is accomplished by hydrophobic interactions and multimerizations. Compounds that inhibit tolaasin toxicity have been isolated from various food additives. Food detergents, sucrose esters of fatty acids, and polyglycerol esters of fatty acids can effectively inhibit tolaasin cytotoxicity. These chemicals, named tolaasin-inhibitory factors (TIF), were effective at concentrations ranging from 10-4 to 10-5 M. The most effective compound, TIF 16, inhibited tolaasin-induced hemolysis independent of temperature and pH, while tolaasin toxicity increased at higher temperatures. When TIF 16 was added to tolaasin-pretreated erythrocytes, the cytotoxic activity of tolaasin immediately stopped, and no further hemolysis was observed. In the artificial lipid bilayer, the single-channel activity of the tolaasin channel was completely and irreversibly blocked by TIF 16. When TIF 16 was sprayed onto pathogen-treated oyster mushrooms growing on the shelves of cultivation houses, the development of disease was completely suppressed, and normal growth of oyster mushrooms was observed. Furthermore, the treatment with TIF 16 did not show any adverse effect on the growth of oyster mushrooms. These results indicate that TIF 16 is a good candidate for the biochemical control of brown blotch disease.

Follow-up of the re-evaluation of polyglycerol esters of fatty acids (E 475) as a food additive.

Polyglycerol esters of fatty acids (PEFA, E 475) was re‐evaluated in 2017 by the former EFSA Panel on Food Additives and Nutrient sources added to Food (ANS). As a follow‐up to this assessment, in this opinion, the Panel on Food Additives and Flavouring (FAF) addresses the data gaps identified to support an amendment of the EU specifications for E 475. The Panel performed a risk assessment of undesirable impurities and constituents potentially present in E 475. The Panel concluded that the maximum limits in the EU specifications for the 4 toxic elements (arsenic, lead, mercury and cadmium) should be lowered based on actual levels in the commercial food additive E 475. The Panel also concluded that maximum limits for erucic acid, 3‐monochloropropanediol and glycidyl esters should be included in the EU specifications for E 475. Alternatively, the Panel recommends an amendment of the definition of E 475 to include a requirement that the fats and oils used in the manufacturing of E 475 comply with the respective EU legislation regarding suitability for human consumption. Further, the Panel concluded that there is no need for setting a specification limit for the content of trans‐fatty acids in E 475 as a limit is established in the Regulation (EU) No 2019/649, i.e. 2 g of trans‐fat per 100 g fat in food for the final consumer. Finally, the Panel recommends a modification of the definition of E 475 indicating that polyglycerol used for the manufacturing of E 475 should be produced from glycerol meeting the specifications for E 422 (Commission Regulation (EU) No 231/2012). In this case, respective specification limits for epichlorohydrin, acrolein and butanetriol would not be needed for E 475.

Characterization and stability of peppermint oil emulsions using polyglycerol esters of fatty acids and milk proteins as emulsifiers.

Three peppermint oil emulsions using polyglycerol esters of fatty acids-casein (PGFE-CN), polyglycerol esters of fatty acids-sodium caseinate (PGFE-NaCN), and polyglycerol esters of fatty acids-whey protein isolate (PGFE-WPI) as emulsifiers were fabricated, and the droplet size, zeta potential, viscosity, and stability of emulsions were determined. The experimental results showed that the emulsion containing PGFE-CN has relatively smaller droplet size of 231.77± 0.49nm. No significant changes were observed on the average particle size, polydispersity index and zeta potential during 4-week of storage, indicating that the emulsions kept stable against pH, salt ion, freeze-thaw, and storage. Fourier transform infrared spectrometer (FTIR) results showed that the electrostatic interaction occurs between CN and PGFE in the emulsion. The confocal laser scanning microscope (CLSM) was used to observe the microstructure of the emulsion, proving that droplets were evenly distributed throughout the aqueous phase by PGFE-CN emulsifier. The protein-stabilized emulsions can be used as potential carriers for the delivery of the lipophilic nutrients such as peppermint oil. PRACTICAL APPLICATION: PGFE-CN emulsifier can be directly added to the beverage systems containing oil or protein, such as coconut milk, peanut milk, and walnut milk. It can enhance the stability of beverage, prevent the precipitation, stratification, and oil floating, improve the homogeneity of the system and therefore extend the shelf life.

A rapid and sensitive method for characterization and quantification of polyglycerol esters by supercritical fluid chromatography coupled to high-resolution mass spectrometry (SFC-HRMS)

Polyglycerol esters of fatty acids (PGEs), a very complex mixture of various isomers, are widely used as green surfactants in different industrial fields such as in cosmetic, pharmaceutic and food industries. However, no study related to the purification and the absolute quantification of these compounds has been described yet. In this study, we developed a rapid and efficient method for characterization and quantification of PGEs using Supercritical Fluid CO2 coupled to High-Resolution Mass Spectrometry (SFC-HRMS). The SFC conditions were first considered including the stationary phase, the nature of mobile phase, the column temperature, the back-pressure regulator. The MS parameters (drying-gas temperature, capillary voltage, nozzle voltage, fragmentor voltage) were then investigated to get the best sensitivity for the PGE analysis. The MS/MS-based structural characterization of targeted PGE, triglycerol mono-oleate (PG3+1C18:1), was established and is helpful to study complex mixtures of PGEs with numerous isobaric PGEs. PG3+1C18:1 was then purified at lab scale and used as standard for quantification. This enabled to develop a rapid quantification method for PG3+1C18:1 within 12 min with good linearity (R2 = 0.9997) as well as sensitivity (picogram level). The validated method was then successfully applied to quantify PG3+1C18:1 in commercial products in order to evaluate their composition.

The Effect of Polyglycerol Esters of Fatty Acids on the Crystallization of Palm Olein.

This research investigated the effect of polyglycerol ester of fatty acids (PGE) on the crystallization of palm olein (POL). Three PGEs were studied: two solid-state PGEs (PGE1105 and PGE1117) and one liquid-state PGE (PGE1155). The addition of 0.5-5% wt. PGEs influenced the crystallization kinetics of POL and this depended on the type and concentration of the emulsifiers. During cooling down with a cooling rate of 5℃/min, the samples containing PGE1105 and PGE1117 started to crystallize at higher temperatures when compared with POL but the crystallization began at lower temperatures for the samples containing PGE1155. All samples with added PGEs exhibited lower solid fat content than that of POL after 12 h of crystallization time. The number of crystals decreased with an increase in the crystal size with PGE addition but there was no effect on polymorphism. Overall, the results suggested that PGE1105 and PGE1117 enhanced the early stages of POL crystallization possibly via the template effects but suppressed the later stages, whereas PGE1155 delayed the whole process of POL crystallization. The application of POL is often limited by its tendency to get cloudy at low temperatures during long-term storage. Based on the results, 1-5% wt. PGE1155 could be used to delay or prevent the crystallization of POL at low temperatures.

Polyglycerol esters of fatty acids as safe and stable matrix forming tableting excipients: A structure-function analysis

This work describes a novel approach for the development of extended release matrix tablets with stable performance via direct compaction. Selected molecules belong to polyglycerol esters of fatty acids (PGFAs) - a group of lipid-based excipients (LBE) with advanced solid-state stability - were used for developing extended release tablets. Metformin HCl as a freely water soluble API was used as model substance. Three PGFA compounds with a HLB range of 1.8–4.5 were selected as matrix forming agents. The deformation behavior of tableting blends with and without PGFAs and their flow properties studied. Blends composing PGFAs showed reduced yield pressure and decreased internal friction between particles, suggesting the tendency to plastic behavior of PGFAs and improved flow properties of their blends, respectively. The blends of selected lipids with API and filler were directly processable via direct compression without any pretreatment such as granulation. The resulted tablets showed desired tensile strength and friability. Application of PGFAs with different HLB allowed the tailoring of API release profile for different time periods with the same concentration of lipid in the tablet. The stable release profile was related to the stable solid state of lipids as matrix agent. No in vitro cytotoxic effect was observed by assessing the dehydrogenase activity.

Co-extruded alginate as an alternative to collagen casings in the production of dry-fermented sausages: Impact of coating composition

The performance of co-extruded alginate coatings containing no extra additives (A), polyglycerol esters of fatty acids (EA), or pea protein (PA) was assessed as an alternative to collagen casings (C) for the manufacturing of dry-fermented sausages (fuet) with no inoculation of moulds and without a fermentation step (NMNF) and fuet inoculated with Penicillium candidum and fermented (MF).Stuffing into collagen casings resulted in slower sausage drying kinetics compared with alginate coating. No significant differences in aw were observed among the studied casing types for NMNF and MF fuets and for the evolution of the technological and spoilage microorganisms. Fuets coated with A, EA, and PA showed lower pH values than fuets stuffed in collagen casings. No significant differences on sensory properties between casing types were observed. Therefore, alginate coatings would be a feasible alternative to collagen casing from a technological and safety point of view.

Novel approach for overcoming the stability challenges of lipid-based excipients. Part 3: Application of polyglycerol esters of fatty acids for the next generation of solid lipid nanoparticles

Solid lipid nanoparticles (SLN) are an advantageous carrier system for the delivery of lipophilic active pharmaceutical ingredients (APIs). The use of SLN has been limited due to stability issues attributed to the unstable solid state of the lipid matrix. A novel approach for overcoming this problem is the application of polyglycerol esters of fatty acids (PGFAs) as lipid matrices with stable solid state. PG2-C18 full, a PGFA molecule, was used to develop SLN loaded with dexamethasone as a model API. Dexamethasone-loaded SLN were manufactured via melt-emulsification and high pressure homogenization in the dosage form of a lipid nanosuspension. SLN with median particle size of 242.1 ± 12.4 nm, zeta potential of −28.5 ± 7.8 mV, entrapment efficiency of 90.2 ± 0.7% and API released after 24 h of 81.7 ± 0.7%, were produced. Differential Scanning Calorimetry (DSC) and Small and Wide Angle X-Ray Scattering (SWAXS) analysis of the lipid nanosuspension evidenced the crystallization of PG2-C18 full in a monophasic system in α-form and absence of polymorphism and crystallite growth up to 6 months storage at room temperature. This resulted in stable performance of the SLN after storage: absence of particle agglomeration, no API expulsion, and stable release profile. The potential pulmonary administration of SLN was tested by the nebulization capacity of the lipid nanosuspension. Cellular exposures to SLN did not induce cytotoxicity or immune effect on pulmonary cells. The application of PGFAs as safe and stable lipid matrices provide a promising approach for the development of the next generation of SLN.

Novel approach for overcoming the stability challenges of lipid-based excipients. Part 2: Application of polyglycerol esters of fatty acids as hot melt coating excipients

The application of hot melt coating (HMC) as an economic and solvent-free technology is restricted in pharmaceutical development, due to the instable solid-state of HMC excipients resulting in drug release instability. We have previously introduced polyglycerol esters of fatty acids (PGFAs) with stable solid-state (Part 1). In this work we showed a novel application of PGFAs as HMC excipients with stable performance. Three PGFA compounds with a HLB range of 5.1–6.2 were selected for developing immediate-release formulations. The HMC properties were investigated. The viscosity of molten lipids at 100 °C was suitable for atomizing. The DSC data showed the absence of low solidification fractions, thus reduced risk of agglomeration during the coating process. The driving force for crystallization of selected compounds was lower and the heat flow exotherms were broader compared to conventional HMC formulations, indicating a lower energy barrier for nucleation and lower crystallization rate. Lower spray rates and a process temperature close to solidification temperature were desired to provide homogeneous coating. DSC and X-ray diffraction data revealed stable solid state during 6 months storage at 40 °C. API release was directly proportional to HLB and indirectly proportional to crystalline network density and was stable during investigated 3 months. Cytotoxicity was assessed by dehydrogenase activity and no in vitro cytotoxic effect was observed.

Novel approach for overcoming the stability challenges of lipid-based excipients. Part 1: Screening of solid-state and physical properties of polyglycerol esters of fatty acids as advanced pharmaceutical excipients

The major challenge of conventional lipid-based excipients (LBE) for drug delivery is their unstable solid state, affecting the stability of pharmaceutical product. Polyglycerol esters of fatty acids (PGFAs) are oligomeric hydroxyethers of glycerol fully or partially esterified with fatty acids. Tuning the number of polyglycerol moieties, fatty acids chain length and free hydroxyl groups per molecule results in diverse physicochemical properties, e.g. HLB, melting point, and wettability, which makes these molecules attractive candidates as novel LBE for different pharmaceutical applications. In this first part of our studies the solid state of PGFAs and the stability thereof were profiled on molecular, nano, and microstructural level and the resulting properties as LBE. DSC analysis confirmed the single phase system of PGFAs without phase separation. WAXS patterns revealed the absence of polymorphism and the direct crystallization into a stable α-form; without transition to more dense configurations. SAXS patterns exposed the lamellar arrangement. The lamellae stacks were characterized by the crystallite thickness and growth. The nano, microstructure and physicochemical properties of PGFAs remained stable during storage. The stable solid state and the broad functionality of PGFAs offer a novel approach to overcome the challenges faced by conventional LBE for advanced pharmaceutical applications. Examples for such applications are presented in the next parts of this study.

Stabilization of the air-liquid interface in sponge cake batter by surface-active proteins and lipids: A foaming protocol based approach

The presence of protein and lipid from wheat flour and eggs at the air-liquid interface (ALI) in sponge cake batter has been studied through a foaming protocol. Sponge cake batter was either prepared from flour, sugar, eggs and leavening agents only or from these ingredients and exogenous lipids (ELs, i.e. a combination of mono- and diacylglycerols and polyglycerol esters of fatty acids). The foaming protocol consisted of whipping diluted sponge cake batter into foam. The foam was considered to be a model for the ALI in sponge cake batter. Foam fractions were then isolated at multiple time points after whipping and chemically analyzed (i.e. lipid and proteins contents and their compositions). In absence of ELs, lipids were not enriched in the foam whereas proteins were. Under such conditions, proteins were more important for stabilizing the ALI than lipids. Size-exclusion high performance liquid chromatography profiles revealed that of all proteins in the system ovalbumin and wheat α- and γ-gliadins had the highest affinity for the ALI. Ovalbumin molecules unfolded and formed intermolecular disulfide bonds at the ALI. Furthermore, flour lipids had higher affinity for the ALI than egg lipids. When ELs were used, foam protein and lipid content and composition essentially remained constant over the experimental time period. In such case, they dominated the ALI and greatly contributed to its stability. Use of ELs decreased batter density and increased batter viscosity, cake volume and cake softness. Hence, it is clear that including ELs in the sponge cake recipe led to high batter and cake quality.

In vitro toxicity screening of polyglycerol esters of fatty acids as excipients for pulmonary formulations

One of the main problems for the development of pulmonary formulations is the low availability of approved excipients. Polyglycerol esters of fatty acids (PGFA) are promising molecules for acting as excipient for formulation development and drug delivery to the lung. However, their biocompatibility in the deep lung has not been studied so far. Main exposed cells include alveolar epithelial cells and alveolar macrophages. Due to the poor water-solubility of PGFAs, the exposure of alveolar macrophages is expected to be much higher than that of epithelial cells. In this study, two PGFAs and their mixture were tested regarding cytotoxicity to epithelial cells and cytotoxicity and functional impairment of macrophages. Cytotoxicity was assessed by dehydrogenase activity and lactate dehydrogenase release. Lysosome function, phospholipid accumulation, phagocytosis, nitric oxide production, and cytokine release were used to evaluate macrophage function. Cytotoxicity was increased with the increased polarity of PGFA molecules. At concentrations above 1 mg/ml accumulation in lysosomes, impairment of phagocytosis, secretion of nitric oxide, and increased release of cytokines were noted. The investigated PGFAs in concentrations up to 1 mg/ml can be considered as uncritical and are promising for advanced pulmonary delivery of high powder doses and drug targeting to alveolar macrophages.

Understanding the effect of emulsifiers on bread aeration during breadmaking.

Much research has been done to explain the action of emulsifiers during breadmaking, but there is still plenty unknown to elucidate their functionality despite their diverse chemical structure. The aim of the present study was to provide some light on the role of emulsifiers on air incorporation into the dough and gas bubbles progress during baking and their relationship with bread features. Emulsifiers like diacetyl tartaric acid ester of monoglycerides (DATEM), sodium stearoyl lactylate (SSL), distilled monoglyceride (DMG-45 and DMG-75), lecithin and polyglycerol esters of fatty acids (PGEF) were tested in very hydrated doughs. Emulsifiers increase the maximum dough volume during proofing. Emulsifiers increase the number of bubbles incorporated during mixing, observing higher number of bubbles, particularly with PGEF. Major changes in dough occurred at 70 K when bubble size augmented, becoming more heterogeneous. DMG-75 produced the biggest bubbles. As a consequence, emulsifiers tend to increase the number of gas cells with lower size in the bread crumb, but led to greater crumb firmness, which suggested different interactions between emulsifiers and gluten, affecting protein polymerization during baking. The progress of the bubbles during baking allowed the differentiation of emulsifiers, which could explain their performance in breadmaking. © 2018 Society of Chemical Industry.

Characteristics and Applications of Oil Solidifying agent using Polyglycerol Esters of Fatty Acids

Characteristics and Applications of Oil Solidifying agent using Polyglycerol Esters of Fatty Acids

Re-evaluation of polyglycerol esters of fatty acids (E475) as a food additive.

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion re‐evaluating the safety of polyglycerol esters of fatty acids (PEFA) (E 475) when used as a food additive. In 1978, the Scientific Committee on Food (SCF) endorsed an acceptable daily intake (ADI) of 25 mg/kg body weight (bw) per day previously established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Absorption of intact PEFA in the gastrointestinal tract was extremely low. PEFA was rapidly and almost fully hydrolysed to polyglycerols and fatty acids in the gastrointestinal tract. The safety of polyglycerols and specific fatty acids has recently been assessed and no adverse effects were identified in the available studies. No adverse effects of PEFA at any dose have been observed in short‐term, subchronic or chronic toxicity studies. A no observed adverse effect level (NOAEL) of 9,000 mg/kg bw per day was identified from subchronic studies and of 2,500 mg/kg bw per day from chronic studies, the highest doses tested. No genotoxic potential of PEFA was identified from the limited information available. The reproductive toxicity studies showed no adverse effects of PEFA but had major limitations. Clinical chemistry and urinalysis, from a clinical study with limited information, did not reveal any adverse effects in volunteers receiving up to 300 mg/kg bw per day for 3 weeks. The highest exposure to PEFA used as a food additive was 2.6 and 6.4 mg/kg bw per day in children at the mean and the 95th percentile, respectively, for the non‐brand loyal scenario. Considering all the above, the Panel concluded that the food additive PEFA (E 475) was not of safety concern at the reported uses and use levels and that there was no need for a numerical ADI. The Panel recommended some modifications of the EU specifications for E 475.

Green Cosmetic Surfactant from Rice: Characterization and Application

During recent years, microwave irradiation has been extensively used for performing green organic synthesis. The aim of this study was to synthesize, through a microwave-assisted irradiation process, a natural surfactant with O/W emulsifying properties. Our attention was focused on polyglycerol esters of fatty acids that are biocompatible and biodegradable non-ionic surfactants widely used in food and cosmetic products. The emulsifier was obtained using vegetable raw material from renewable sources: polyglycerol derived from vegetable glycerol and rice bran oil fatty acids. The natural emulsifier obtained was then characterized and evaluated for its emulsifying properties using different doses, oil phases, rheological additives, waxes, etc. The potential application in solar products, in comparison with other natural emulsifiers, was also evaluated.

Synthesis Characterization and Application of Polyglycerol Esters of Fatty Acids: Biodegradable Surfactants

Surfactant-based separations are attracting interest due to simple operations and viable economics. The present work focuses on the synthesis of two nonionic surfactants, polyglycerol fatty acid esters of cotton seed oil and castor seed oil, its characterization using Fourier transform infrared spectroscopy and liquid spectroscopy-mass spectroscopy. The synthesized surfactant is used in breaking azeotropic composition of n-propanol–water mixture via cloud point separation. The separation obtained from the synthesized surfactants is compared with the separation obtained from Tween 20 and it is found that both the synthesized surfactants are capable of breaking the azeotrope of n-propanol–water mixture.

Estimation of the dietary intake of 13 priority additives in France, Italy, the UK and Ireland as part of the FACET project

The aim of this study was to assess the dietary exposure of 13 priority additives in four European countries (France, Italy, the UK and Ireland) using the Flavourings, Additives and Contact Materials Exposure Task (FACET) software. The studied additives were benzoates (E210–213), nitrites (E249–250) and sulphites (E220–228), butylated hydroxytoluene (E321), polysorbates (E432–436), sucroses esters and sucroglycerides (E473–474), polyglycerol esters of fatty acids (E475), stearoyl-lactylates (E481–482), sorbitan esters (E493–494 and E491–495), phosphates (E338–343/E450–452), aspartame (E951) and acesulfame (E950). A conservative approach (based on individual consumption data combined with maximum permitted levels (Tier 2)) was compared with more refined estimates (using a fitted distribution of concentrations based on data provided by the food industry (Tier 3)). These calculations demonstrated that the estimated intake is below the acceptable daily intake (ADI) for nine of the studied additives. However, there was a potential theoretical exceedance of the ADI observed for four additives at Tier 3 for high consumers (97.5th percentile) among children: E220–228 in the UK and Ireland, E432–436 and E481–482 in Ireland, Italy and the UK, and E493–494 in all countries. The mean intake of E493–494 could potentially exceed the ADI for one age group of children (aged 1–4 years) in the UK. For adults, high consumers only in all countries had a potential intake higher than the ADI for E493–494 at Tier 3 (an additive mainly found in bakery wares). All other additives examined had an intake below the ADI. Further refined exposure assessments may be warranted to provide a more in-depth investigation for those additives that exceeded the ADIs in this paper. This refinement may be undertaken by the introduction of additive occurrence data, which take into account the actual presence of these additives in the different food groups.

Effects of polyglycerol esters of fatty acids and ethylene‐vinyl acetate co‐polymer on crystallization behavior of biodiesel

AbstractBiodiesel fuels (BDF) have many problems in the cold due to their crystallization properties. In particular, precipitation of large crystals of high‐melting fractions in BDF at low temperatures remarkably changes cold flow property of BDF and, thereby, it increases the values of cold filter plugging point. In this study, we evaluated polyglycerol esters of fatty acids (PGE) and ethylene‐vinyl acetate co‐polymer (EVA) as chemical additives to improve the cold flow property of palm oil‐based FAME (PFME). The results of solid fat content measurement indicate that the simultaneous addition of PGE and EVA showed synergistic effects on suppression of crystallization of PFME, however such effect was not observed when EVA was used alone. DSC thermograms indicated that the PGE additives not only decreased the crystallization temperature but also kinetically suppressed the crystal growth. Polarized light microscopy showed that the simultaneous addition of PGE and EVA led to the formation of considerably small and fine‐dispersed crystals of PFME. These results indicate that combined effects of PGE and EVA caused the formation of fine‐dispersed PFME crystals, which could improve the viscous properties of palm oil‐based BDF at relatively cold temperatures.