Compendium of the most significant studies with reference to properties, intake, effects.
Ballmann C, Mueller BW. Stabilizing effect of cetostearyl alcohol and glyceryl monostearate as co-emulsifiers on hydrocarbon-free O/W glyceride creams. Pharm Dev Technol. 2008;13(5):433-45. doi: 10.1080/10837450802247952.
Abstract. The structure of a stable O/W cream is characterized by a more or less pronounced mixed crystal bilayer. The addition of co-emulsifiers in order to achieve a soft formulation often leads to a mixed crystal bilayer network of high viscosity and even phase separation. In order to ovoid this components of different chemical identities are used which often are not inert or harmless if they are absorbed. For this reason it seems to be interesting to use only components from one chemical family, e.g. to use only glycerides and their derivatives because in the case of absorption they are metabolized. The disadvantages of glyceride creams are, however, their low viscosity. The aim of this investigation was to find the optimum amount of co-emulsifier as consistency excipient for the basic formulation of an O/W glyceride cream. This was achieved by using differential scanning calorimetry; thermogravimetry, oscillation rheology and various stress tests. The amount of co-emulsifier used should not be too high, as it would crystallize increasingly during storage which gives the preparation an optical inhomogenity and a lack in softness which is needed for a suitable cosmetic acceptance. A slightly higher concentration than is necessary for the mixed emulsifier system can be advantageous, as the formation of a separate crystalline lipophilic network in the preparation increases its viscosity which will lead to a higher physico-chemical stability of the formulation. These results were obtained with the co-emulsifiers glyceryl monostearate (Imwitor 900), cetylstearyl alcohol (Lanette O), and PEG-20-glycerolstearate (Tagat S2) as O/W emulsifier. As oil phase a mixture of Miglyol 812 (caprylic/capric triglyceride) and Avocado oil was used.
Huang S, He J, Cao L, Lin H, Zhang W, Zhong Q. Improved Physicochemical Properties of Curcumin-Loaded Solid Lipid Nanoparticles Stabilized by Sodium Caseinate-Lactose Maillard Conjugate. J Agric Food Chem. 2020 Jul 1;68(26):7072-7081. doi: 10.1021/acs.jafc.0c01171.
Abstract. To improve the water solubility, antioxidant activity, and chemical stability of curcumin, solid lipid nanoparticles (SLNs) were fabricated using equal masses of propylene glycol monopalmitate and glyceryl monostearate as the lipid matrix and sodium caseinate-lactose (NaCas-Lac) Maillard conjugate as the emulsifier. The entrapment efficiency was more than 90% when curcumin was 2.5% and 5.0% of lipid mass, and the SLNs were stable during 30-day storage. SLNs stabilized by NaCas-Lac showed better physicochemical properties than those prepared with NaCas, including higher sphericity and homogeneity; higher entrapment efficiency; better stability against pH, ionic strength, and simulated gastrointestinal digestions; and more controlled release. SLNs also greatly enhanced the antioxidant activity of encapsulated curcumin and the retention of curcumin during storage. Therefore, the present SLNs may find applications to deliver lipophilic compounds in functional foods and beverages.
López-Iglesias C, López ER, Fernández J, Landin M, García-González CA. Modeling of the Production of Lipid Microparticles Using PGSS® Technique. Molecules. 2020 Oct 24;25(21):4927. doi: 10.3390/molecules25214927.
Abstract. Solid lipid microparticles (SLMPs) are attractive carriers as delivery systems as they are stable, easy to manufacture and can provide controlled release of bioactive agents and increase their efficacy and/or safety. Particles from Gas-Saturated Solutions (PGSS®) technique is a solvent-free technology to produce SLMPs, which involves the use of supercritical CO2 (scCO2) at mild pressures and temperatures for the melting of lipids and atomization into particles. The determination of the key processing variables is crucial in PGSS® technique to obtain reliable and reproducible microparticles, therefore the modelling of SLMPs production process and variables control are of great interest to obtain quality therapeutic systems. In this work, the melting point depression of a commercial lipid (glyceryl monostearate, GMS) under compressed CO2 was studied using view cell experiments. Based on an unconstrained D-optimal design for three variables (nozzle diameter, temperature and pressure), SLMPs were produced using the PGSS® technique. The yield of production was registered and the particles characterized in terms of particle size distribution. Variable modeling was carried out using artificial neural networks and fuzzy logic integrated into neurofuzzy software. Modeling results highlight the main effect of temperature to tune the mean diameter SLMPs, whereas the pressure-nozzle diameter interaction is the main responsible in the SLMPs size distribution and in the PGSS® production yield.
Yoshida T, Sako K, Kondo H. Design of novel tacrolimus formulations with chemically synthesized oils for oral lymphatic delivery. Drug Dev Ind Pharm. 2020 Feb;46(2):219-226. doi: 10.1080/03639045.2020.1721525.
Abstract. High consumption of oil formulations has been reported to reduce the blood exposure of drugs like tacrolimus. Consumption of oil formulations has also been shown to inhibit T-cell production of interleukin-2 (IL-2) compared to solid dispersion formulations (SDFs). However, a large amount of oil causes gastrointestinal side effects such as diarrhea and low compliance. Here, we investigated the feasibility of reducing the amount of oil and substitution of chemically synthetized oils for natural oils in these formulations. Reducing the amount of sunflower oil increased blood tacrolimus exposure despite sufficient suppression of IL-2 production. While medium-chain triglyceride (MCT) increased tacrolimus blood exposure, addition of 10% glyceryl monostearate (GMS) to MCT significantly decreased drug blood exposure without requiring a large amount of oil (p < .05). Effects of the contents of GMS in the MCT/GMS formulations, and fatty acid composition in GMS on drug blood exposure were also investigated. The results indicated that both the amount and type of oil were important for maintaining a good balance between a reduction in blood exposure and sufficient IL-2 suppression. The ratio of drug concentration in lymphocytes to that in whole blood after dosing with an oil formulation was significantly higher than that after administration of the SDF (p < .01). These results indicate the feasibility of developing oral oil tacrolimus formulations to reduce systemic side effects and maintain high efficacy for practical use in patients.
Affram KO, Smith T, Ofori E, Krishnan S, Underwood P, Trevino JG, Agyare E. Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells. J Drug Deliv Sci Technol. 2020 Feb;55:101374. doi: 10.1016/j.jddst.2019.101374.
Abstract. This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween® 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN15 was selected based on entrapment efficiency (EE) of Gem, loading efficiency of Gem, cytotoxicity and rate of Gem release. Growth inhibition of Gem-SLN15-treated PPCL-46 culture (IC50 (2D) =27± 5 μM; IC50 (3D) = 66 ± 2 μM) was remarkably higher than gemcitabine hydrochloride (GemHCl)-treated PPCL-46 culture (IC50 (2D) =126±3 μM; IC50 (3D) =241±3 μM). Similar trend of higher Gem-SLN15 inhibition in MiaPaCa-2 culture was found (IC50 (2D) =56±16 μM; IC50 (3D) =127±4 μM) compared with GemHCl-treated Mia-PaCa-2 culture (IC50 (2D) =188±46 μM; IC50 (3D) =254±52 μM). The anticancer activity of Gem-SLN15 was significantly more effective than GemHCl in PPCL-46 compared to Mia-PaCa-2 cancer cells. Schematic diagram for preparation of Gem-SLN through cold homogenization and methods for characterization and in-vitro studies.
Herazo MÁ, Ciro-Velásquez HJ, Márquez CJ. Rheological and thermal study of structured oils: avocado (Persea americana) and sacha inchi (Plukenetia volubilis L.) systems. J Food Sci Technol. 2019 Jan;56(1):321-329. doi: 10.1007/s13197-018-3492-4.
Abstract. Rheological and thermal characterization was performed in emulsions formulated from avocado oil and sacha inchi oil structured with soy lecithin, glyceryl monostearate and shortening (palm oil). For oleogel formulations, a completely randomized factorial design was considered to study the effect of the type of emulsifier and the proportions of avocado and sacha inchi oils. The rheological results indicated pseudoplastic behavior with semisolid characteristics. Additionally, the phase change studies showed two endothermic events corresponding to melting points from - 20.15 to - 18.94 °C and from 40.25 to 61.04 °C. The formulation with a ratio of avocado oil to sacha inchi oil of 80/20 and prepared using glyceryl monostearate as an emulsifier was evaluated as the best treatment and had an increased consistency coefficient and an increased loss tangent (δ < 0.5).
Uyama M, Araki H, Fukuhara T, Watanabe K. Physicochemical Properties of α-Form Hydrated Crystalline Phase of 3-(10-Carboxydecyl)-1,1,1,3,5,5,5-heptamethyl Trisiloxane/Higher alcohol/Polyoxyethylene (5 mol) Glyceryl monostearate/Water System. J Oleo Sci. 2018 Jul 1;67(7):839-849. doi: 10.5650/jos.ess17279.
Abstract. The α-form hydrated crystalline phase (often called as an α-gel) is one of the hydrated crystalline phases which can be exhibited by surfactants and lipids. In this study, a novel system of an α-form hydrated crystal was developed, composed of 3-(10-carboxydecyl)-1,1,1,3,5,5,5-heptamethyl trisiloxane (CDTS), polyoxyethylene (5 mol) glyceryl monostearate (GMS-5), higher alcohol. This is the first report to indicate that a silicone surfactant can form an α-form hydrated crystal. The physicochemical properties of this system were characterized by small and wide angle X-ray scattering (SWAXS), differential scanning calorimetry (DSC), and diffusion-ordered NMR spectroscopy (DOSY) experiments. SWAXS and DSC measurements revealed that a plurality of crystalline phases coexist in the CDTS/higher alcohol/water ternary system. By adding GMS-5 to the ternary system, however, a wide region of a single α-form hydrated crystalline phase was obtained. The self-diffusion coefficients (Dsel) from the NMR measurements suggested that all of the CDTS, GMS-5, and higher alcohol molecules were incorporated into the same α-form hydrated crystals.
Cabrera S, Rojas J. Rheological, thermal, and microstructural data of lemon essential oil structured with fatty gelators. Data Brief. 2020 Jul 12;31:106014. doi: 10.1016/j.dib.2020.106014.
Su W, Polyakov NE, Xu W, Su W. Preparation of astaxanthin micelles self-assembled by a mechanochemical method from hydroxypropyl β-cyclodextrin and glyceryl monostearate with enhanced antioxidant activity. Int J Pharm. 2021 Aug 10;605:120799. doi: 10.1016/j.ijpharm.2021.120799.
Ferro AC, de Souza Paglarini C, Rodrigues Pollonio MA, Lopes Cunha R. Glyceryl monostearate-based oleogels as a new fat substitute in meat emulsion. Meat Sci. 2021 Apr;174:108424. doi: 10.1016/j.meatsci.2020.108424.
Glyceryl stearate 
