Encapsulation of Active Pharmaceutical Ingredients in Lipid Micro/Nanoparticles for Oral Administration by Spray-Cooling.

Nanoencapsulation via spray cooling (also known as spray chilling and spray congealing) has been used with the aim to improve the functionality, solubility, and protection of drugs; as well as to reduce hygroscopicity; to modify taste and odor to enable oral administration; and many times to achieve a controlled release profile. It is a relatively simple technology, it does not require the use of low-cost solvents (mostly associated to toxicological risk), and it can be applied for lipid raw materials as excipients of oral pharmaceutical formulations. The objective of this work was to revise and discuss the advances of spray cooling technology, with a greater emphasis on the development of lipid micro/nanoparticles to the load of active pharmaceutical ingredients for oral administration.

Tailoring Properties of Mixed-Component Oleogels: Wax and Monoglyceride Interactions Towards Flaxseed Oil Structuring.

The combination of oleogelators in oil structuring has an untapped potential, since effective pairs have usually been found by serendipity. The aim of this work was to evaluate the combination of berry (BEW) or sunflower wax (SHW) with glycerol monostearate (GMS) in flaxseed oil (FXO) at 5 and 25 °C. The thermal and mechanical properties, microstructure, and stability of oleogels were investigated. Self-standing and translucent gels were obtained from BEW in FXO. However, the mixture BEW:GMS resulted in a decrease of dynamic moduli. Moreover, changes in the crystal network and a reduction of oil binding capacity were noticed. Thus, the GMS prevented the complete organization of BEW in polyunsaturated chains of FXO. Conversely, a positive interaction was found for GMS:SHW, since both alone were not able to impart the structure in FXO. Interestingly, gel was formed with improved properties, even with a small addition of GMS, although an ideal ratio of 1:1 (GMS50:50SHW) was found. Oxidative stability analysis showed that all gels resembled the behavior of liquid oil (~12.00 meqO2/kg) over 30 days storage. Therefore, semi-solid systems with nutritional and techno-functional claims were created by using waxes and fatty-acid derivative oleogelator in a rational fashion; this opened the opportunity to tailor oleogel properties.

Formation and stability of W/O-high internal phase emulsions (HIPEs) and derived O/W emulsions stabilized by PGPR and lecithin.

Water-in-oil high internal phase emulsions (HIPEs) can provide interesting textures that could be used to reduce trans- and/or saturated fat content in food products. On the other hand oil-in-water emulsions can be found in a variety of food and beverages. Moreover, strategies aiming synthetic or semi-synthetic ingredients replacement by natural alternatives for food applications has been pursuit. For these purposes, the effect of partial replacement of PGPR by lecithin on properties of either W/O-HIPEs or O/W emulsions manufactured from the same initial composition but showing different volume fraction of dispersed phase were investigated aiming to understand the behaviour of emulsifiers' mixture in water-oil or oil-water interfaces. Firstly, water-in-oil HIPEs were produced using a rotor-stator device. At fixed total amount of emulsifier (2% w/w), W/O emulsions stabilized with LEC:PGPR ratios of 0.5:1.5 and 1.0:1.0 showed similar droplet size with a better kinetic stability compared to emulsions containing only PGPR. These results indicated good interaction between LEC and PGPR, which was also confirmed by dynamic interfacial tension profile and interfacial dilational rheology. In order to reduce the droplet size of W/O-HIPEs, these emulsions were subsequently subjected to high-pressure homogenization and interestingly phases inversion was observed. Confocal microscopy confirmed the phases inversion attributed to high input of energy leading to the formation of O/W emulsions. Then both W/O-HIPEs and O/W emulsions were investigated regarding LEC:PGPR mixtures as emulsifiers. All W/O-HIPEs showed shear thinning behavior and high viscosity at low shear rate whereas O/W emulsions showed low viscosity and Newtonian behavior. The increase of lecithin content in emulsifier mixture led to more stable O/W emulsions, whereas more stable W/O-HIPEs were produced by lecithin and PGPR mixtures ratio of 0.5:1.5 and 1.0:1.0.

Lecithin and phytosterols-based mixtures as hybrid structuring agents in different organic phases.

In this study the effect of lecithin (L) addition and solvent quality in a well-established oleogel system formed by ß-sitosterol and γ-oryzanol (BG) was investigated. Medium chain triglycerides (MCT) and sunflower oil (SFO) were used as triglycerides and hexadecane (HEX) as a model of linear hydrocarbon. Lecithin was proposed due to its natural and versatile properties, showing different functionalities such as emulsifier and co-oleogelator. A study based on hierarchical organization of structured oil was performed applying techniques for bulk, meso and nanoscale. Self-sustained structures could no longer be observed after 40 wt% of BG replacement by lecithin. Small-angle X-ray scattering showed that the formed nanostructures (building blocks) were dependent on type of solvent and BG:L ratio in the mixture of oleogelators. Differential scanning calorimetry showed that stability against temperature was improved decreasing the polarity of the oil, and a time-dependent self-assembly of hybrid systems was observed from thermal and rheological measurements. Microscopy images exhibited changes on typical fibril aggregation of BG as lecithin was added, which promoted to a certain extent the suppression of ribbons. Oscillatory shear and uniaxial compression measurements were influenced by BG:L ratio and solvent mainly at higher lecithin amount. The combination of BG and MCT appeared to be the most affected by lecithin incorporation whereas SFO rendered harder oleogels. These results could contribute to understand the role of both lecithin and solvent type influencing the host oleogelator structure. It was hypothesized that intermolecular BG complex formation is hindered by lecithin, besides this phospholipid also might coexist as a different phase, causing structural changes in the gel network. Addressing the role of co-oleogelator it can provide the opportunity to tune soft materials with adjusted properties.

Synergistic interactions between lecithin and fruit wax in oleogel formation.

In this study, the effect of lecithin (LEC) on the crystallization and gelation of fruit wax (FW) with sunflower oil was researched. A synergistic effect on the gel strength was observed at FW : LEC ratios of 75 : 25 and 50 : 50, compared to the corresponding single component formulations (100 : 0 and 0 : 100). Even below the critical gelling concentration (Cg) of FW, the addition of lecithin enabled gel formation. Lecithin affected the thermal behavior of the structure by delaying both crystallization and gel formation. The phospholipid acted as a crystal habit modifier changing the microstructure of the oleogel, as was observed by polarized light microscopy. Cryo-scanning electron microscopy revealed a similar platelet-like arrangement for both FW as a single oleogelator and FW in combination with LEC. However, a denser structure could be observed in the FW : LEC oleogelator mixture. Both the oil-binding capacity and the thixotropic recovery were enhanced upon lecithin addition. These improvements were attributed to the hydrogen bonding between FW and LEC, as suggested by Raman spectroscopy. We hypothesized that lecithin alters the molecular assembly properties of the FW due to the interactions between the polar moieties of the oleogelators, which consequently impacts the hydrophobic tail (re)arrangement in gelator-gelator and solvent-gelator interactions. The lipid crystal engineering approach followed here offered prospects of obtaining harder self-standing structures at a lower oleogelator concentration. These synergistic interactions provide an opportunity to reduce the wax concentration and, as such, the waxy mouthfeel without compromising the oleogel properties.