Modulation of the crystallization of rapeseed oil using lipases and the impact on ice cream properties.

We investigated the possibility to use rapeseed as a main oil in ice cream formulations by changing its functionality when using different kinds of lipases. Through a 24 h-emulsification and a centrifugation, the modified oils were further used as functional ingredients. All lipolysis was first assessed as a function of time by 13C NMR, where triglycerides consumption and the formation of low-molecular polar lipids (LMPL: monoacylglycerol and free fatty acids, FFAs) were selectively identified and compared. The more the FFAs, the sooner the crystallization (from -55 to -10 °C) and the later the melting temperatures (from -17 to 6 °C) measured by differential scanning calorimetry. These modifications were exploited in ice cream formulations with a significant impact on overall hardness (range of 60-216 N) and flowing during defrosting (from 1.29 to 0.35g/min). The global behavior of products can be controlled by the composition of LMPL within oil.

Study of rapeseed oil gelation induced by commercial monoglycerides using a chemometric approach.

Commercial oleogelators rich in monoglycerides (MGs) are complex mixtures of acylglycerides with variable gelling properties, depending on the oil used and their concentration. In this study we developed a chemometric approach to identify the key parameters involved in gelling process. Analytical parameters have been defined, using GC and NMR analysis to identify fatty acids and acylglycerides composing the mixtures. Specific acylglyceride families and compound ratios were calculated to streamline the analytical results. To determine the key analytical parameters, artificial neural networks were used in a QSPR study related to the gelling properties measured by rheology through oscillatory experiments. At low oleogelator concentrations, the MGs especially rich in C16:0 and the ratio of specific isomers both have a positive influence on G'. For high oleogelator concentrations, C18:0-rich acylglycerides and unsaturated/saturated fatty acid ratios have a positive influence on G'. Conversely, at low concentrations, C18:0-rich acylglycerides show a lesser effect on G'.

Organogel Nanoparticles as a New Way to Improve Oral Bioavailability of Poorly Soluble Compounds.

PURPOSE: The aim of the study was to evaluate organogel nanoparticles as a lipophilic vehicle to increase the oral bioavailability of poorly soluble compounds. Efavirenz (EFV), a Biopharmaceutical Classification System (BCS) Class II, was used as drug model. METHODS: Organogel nanoparticles loaded with EFV were formulated with sunflower oil, 12-hydroxystearic acid (HSA) and polyvinyl alcohol (PVA). Various parameters have been investigated in the current study such as (i) the release profile of organogel assessed by USP 4 cell flow dialysis, (ii) the impact of organogel on intestinal absorption, using Caco-2 cells as in vitro model and jejunum segments as ex vivo assay and (iii) the bioavailability of organogel following oral pharmacokinetic study. RESULTS: 250-300 nm spherical particles with a final concentration of 4.75 mg/mL drug loading were obtained, corresponding to a thousand fold increase in EFV solubility, combined to a very high encapsulation efficiency (>99.8%). Due to rapid diffusion, drug was immediately released from the nanoparticles. The biopharmaceutical evaluation on ex vivo jejunum segments demonstrated an increased absorption of EFV from organogel nanoparticles compare to a native EFV suspension. In vitro assays combining Caco-2 cell cultures with TEM and confocal microscopy demonstrated passive diffusion, while paracellular integrity and endocytosis activity remain expelled. Oral pharmacokinetics of EFV organogel nanoparticles improve oral bioavailability (Fr: 249%) and quick absorption compared to EFV suspension. CONCLUSION: Organogel nanoparticles increase the bioavailability of BCS Class II drugs. The main phenomena is simply oil transfer from the gelled particles through the cell membrane.

How an organogelator can gelate water: gelation transfer from oil to water induced by a nanoemulsion.

A hydrogel can be formed by an organogelator in the presence of a nanoemulsion. It is expected that this is due to a gelation transfer from oil to water. The system started with an oil-in-water nanoemulsion prepared according to a phase inversion temperature (PIT) process. Into this nanoemulsion consisting of Kolliphor® RH40 and Brij® L4 as surfactants, and Miglyol® 812 as oil and water, we introduced the organogelator 12-hydroxyoctadecanoic acid (12-HOA) in the oil phase. After cooling at room temperature, a slow reversible gelation of the water phase occurred with persistence of the nanoemulsion. This thermally reversible system was investigated using various techniques (rheology, turbidimetry, optical and electron microscopies, scattering techniques). Successive stages appeared during the cooling process after the nanoemulsion formation, corresponding to the migration and self-assembly of the organogelator from the oil nanodroplets to the water phase. According to our measurements and the known self-assembly of 12-HOA, a mechanism explaining the formation of the gelled nanoemulsion is proposed.

Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds.

The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.

Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug.

This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol-gel-sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer-Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium.

Micelle-vesicle transition of fatty acid based ion-pair surfactants: interfacial evidence and influence of the ammonium counterion structure.

We describe the synthesis and the physicochemical study of new ion-pair amphiphiles from a mixture of bicyclic, cyclic, linear or branched amines and fatty acids of three chain lengths. Surface-tension measurements of bicyclic, cyclic and branched structures of ammonium/alkanoate acid ion pairs show a phase transition, with two plateaux in the plot of surface tension versus log(c) (c=concentration). Such behaviour is related to the structure of the counterion, the alkyl chain length and the temperature. Pulsed gradient spin echo NMR spectroscopy experiments were performed to demonstrate the existence of micelles on the first plateau and to confirm the phase transition. The existence of vesicles on the second plateau of the surface tension was proved by CryoTEM observation and dynamic light scattering (DLS) measurements. Mainly, according to the structure of the counterion, there is either a strong association and a positioning along the chain leading to vesicles or a less strong association leading to external positioning and the formation of micelles at low concentrations or vesicles at higher concentrations.