Formation of Microcapsules of Pullulan by Emulsion Template Mechanism: Evaluation as Vitamin C Delivery Systems.

Pullulan is a polysaccharide that has attracted the attention of scientists in recent times as a former of edible films. On the other hand, its use for the preparation of hydrogels needs more study, as well as the formation of pullulan microcapsules as active ingredient release systems for the food industry. Due to the slow gelation kinetics of pullulan with sodium trimetaphosphate (STMP), capsules cannot be formed through the conventional method of dropping into a solution of the gelling agent, as with other polysaccharides, since the pullulan chains migrate to the medium before the capsules can form by gelation. Pullulan microcapsules have been obtained by using inverse water-in-oil emulsions as templates. The emulsion that acts as a template has been characterized by monitoring its stability and by optical microscopy, and the size of the emulsion droplets has been correlated with the size of the microcapsules obtained, demonstrating that it is a good technique for their production. Although some flocs of droplets form, these remain dispersed during the gelation process and two capsule size distributions are obtained: those of the non-flocculated droplets and the flocculated droplets. The microcapsules have been evaluated as vitamin C release systems, showing zero-order release kinetics for acidic pH and Fickian mechanism for neutral pH. On the other hand, the microcapsules offer good protection of vitamin C against oxidation during an evaluation period of 14 days.

Rheological Study of the Formation of Pullulan Hydrogels and Their Use as Carvacrol-Loaded Nanoemulsion Delivery Systems.

Hydrogels have been extensively studied as delivery systems for lipophilic compounds. Pullulan hydrogels were prepared, and their gelation kinetics were studied over time. Pullulan exhibited a relatively slow gelling reaction in basic medium (KOH) using trisodium metaphosphate (STMP) as a cross-linking agent, so capsules cannot be obtained by dripping as easily as in the case of alginate and chitosan. The kinetics of pullulan gelation were studied through rheological analysis over time. An optimal [Pullulan]/[KOH] ratio was found for a fixed [Pullulan]/[STMP] ratio. For this given relationship, gelling time measurements indicated that when the concentration of pullulan increased, the gelation time decreased from 60 min for 6% w/w pullulan to 10 min for 10% w/w. After the gel point, a hardening of the hydrogel was observed over the next 5 h. The formed hydrogels presented high degrees of swelling (up to 1800%). Freeze-dried gels were capable of being rehydrated, obtaining gels with rheological characteristics and visual appearance similar to fresh gels, which makes them ideal to be freeze-dried for storage and rehydrated when needed. The behavior of the hydrogels obtained as active ingredient release systems was studied. In this case, the chosen molecule was carvacrol (the main component of oregano oil). As carvacrol is hydrophobic, it was incorporated into the droplets of an oil-in-water nanoemulsion, and the nanoemulsion was incorporated into the hydrogel. The release of the oil was studied at different pHs. It was observed that as the pH increased (from pH 2 to pH 7), the released amount of carvacrol for the gel with pullulan 10% w/w reached 100%; for the other cases, the cumulative release amount was lower. It was attributed to two opposite phenomena in the porous structure of the hydrogel, where more porosity implied a faster release of carvacrol but also a higher degree of swelling that promoted a higher entry of water flow in the opposite direction. This flow of water prevented the active principle from spreading to the release medium.

Study of nanoemulsions using carvacrol/MCT-(Oleic acid-potassium oleate)/ Tween 80 ®- water system by low energy method.

Carvacrol is studied in different fields due to its microbial and antioxidant properties. Its use is limited because of the water insolubility and its strong taste. To overcome these problems, carvacrol has been successfully loaded into nanoemulsions. The low-energy emulsification method Phase Inversion Composition (PIC) is used to prepare oil-in-water nanoemulsions in the carvacrol/medium chain triglycerides (MCT)-(oleic acid-potassium oleate/Tween 80 ®)-water system. Oleic acid acts as a co-surfactant when it is neutralized with KOH along the emulsification path changing the spontaneous curvature of the interface when increasing the HLB number from 1 for the oleic acid to 20 for the potassium oleate and, therefore, changing the HLB number of the surfactant mixture. The phases diagrams are studied in order to understand the behaviour of the system and to establish the composition range where nanoemulsions can be obtained. Nanoemulsions are formed when the emulsification path crosses a region of direct or planar structure without excess of oil. Experimental design is performed in order to study the influence of composition variables as carvacrol/MCT ratio and (oleic-oleate)/Tween 80 ® ratio (OL-OT/T80 ratio) on the diameter of the nanoemulsions and their stability. It has been observed the importance of the HLB number of the surfactants mixture in order to obtain small-sized stable nanoemulsions. Surface response graphic shows that (OL-OT)/T80 ratio is a significant parameter in the mean diameter of the nanoemulsions. A minimum diameter is obtained for a (OL-OT)/T80 ratio 45/55 due to the fact that ratio is near the preferred HLB of the oil mixture and the emulsification path contains a wide liquid crystal monophasic region with all the oil incorporated in the structure. Diameters of 19 nm for carvacrol/MCT ratio of 30/70 or diameters of 30 nm for ratios of 45/55 with high stability values presented a good potential to be incorporated into edible films in the future. Regarding nanoemulsions stability an optimum value is also observed for a carvacrol/MCT ratio. The addition of another carrier oil as olive oil instead of MCT showed an improvement of the nanoemulsions stability against Ostwald ripening, probably due to the smaller solubility of olive oil. The use of olive oil does not significantly change the diameter of the nanoemulsion.

Encapsulation of Carvacrol-Loaded Nanoemulsion Obtained Using Phase Inversion Composition Method in Alginate Beads and Polysaccharide-Coated Alginate Beads.

Nanoemulsions have been widely studied as lipophilic compound loading systems. A low-energy emulsification method, phase inversion composition (PIC), was used to prepare oil-in-water nanoemulsions in a carvacrol-coconut oil/Tween 80®-(linoleic acid-potassium linoleate)/water system. The phase behaviour of several emulsification paths was studied and related to the composition range in which small-sized stable nanoemulsions could be obtained. An experimental design was carried out to determine the best formulation in terms of size and stability. Nanoemulsions with a very small mean droplet diameter (16-20 nm) were obtained and successfully encapsulated to add carvacrol to foods as a natural antimicrobial and antioxidant agent. They were encapsulated into alginate beads by external gelation. In order to improve the carvacrol kinetics release, the beads were coated with two different biopolymers: chitosan and pullulan. All formulations were analysed with scanning electron microscopy to investigate the surface morphology. The release patterns at different pHs were evaluated. Different kinetics release models were fitted in order to study the release mechanisms affecting each formulation. Chitosan-coated beads avoided the initial release burst effect, improving the beads' structure and producing a Fickian release. At basic pH, the chitosan-coated beads collapsed and the pullulan-coated beads moderately improved the release pattern of the alginate beads. For acid and neutral pHs, the chitosan-coated beads presented more sustained release patterns.

Use of Double Gelled Microspheres to Improve Release Control of Cinnamon-Loaded Nanoemulsions.

The use of nanoemulsions as encapsulation systems for active ingredients, such as cinnamon oil, has been studied. A surfactant based on polyoxyethylene glycerol esters from coconut/palm kernel oil has been used. The nanoemulsions were obtained by the two most commonly low-energy emulsification methods, the composition inversion phase (PIC) and the temperature inversion phase (PIT) methods. Nanoemulsions were successfully obtained by both methods, with very small droplet sizes (5-14 nm) in both cases, but a greater stability was observed when the PIT method was used. Nanoemulsions were encapsulated by external gelation using two different polysaccharides, alginate or chitosan, dissolved in the continuous phase of the nanoemulsion. Then, the nanoemulsion was dropped into a bath with a gelling agent. To improve the release control of cinnamon oil and avoid the burst effect, beads prepared with one of the polysaccharides were coated with the second polysaccharide and then gelled again. Double gelled beads were successfully obtained, the core with chitosan and the outer layer (shell) with alginate. SEM images showed the morphology of the single beads presenting high porosity. When the beads were coated, the porosity decreased because the second polysaccharide molecules covered the pre-existing pores. The smoother surface was obtained when this second layer was, in turn, gelled. The release patterns at pH = 2 and pH = 7 were studied. It was observed that the double gelled bead provided a more gradual release, but maintained approximately the same amount of final released oil. The release patterns were fitted to the Korsmeyer-Peppas model. The fitting parameters reflected the effect of the different coating layers, correlating with different diffusion mechanisms according to the bead core and shell materials.

Rheology of water-in-water emulsions: Caseinate-pectin and caseinate-alginate systems.

Conventional models developed for oil-water emulsions do not fit viscosity of caseinate-pectin and caseinate-alginate water-in-water emulsions, which is always lower than predicted, except for high viscosities of disperse phase. These models do not consider strong deformations, prevented by the high interfacial tension of oil-water interphases. The ultra-low interfacial tension of water-in-water emulsions facilitates the creation of interphase and very elongated droplets. Capron model considers interfacial tension, fitting results when the dispersed phase is the most viscous, but, for other cases, lower experimental values are obtained related to the shear-induced stratification. Even values below the stratification model are observed for some samples, related to the influence of the interphase in the viscosity of the emulsion. A model that takes into account the presence of a relatively thick interphase poor in both polymers is proposed. Intermediate structures between highly elongated and stratified fluids, with influence of interphase viscosity could explain results.

Type and doses of oral anticoagulants and adherence to anticoagulant treatment in elderly patients with atrial fibrillation: the ESPARTA study.

AIM: To analyze the use of oral anticoagulants in elderly patients with atrial fibrillation in clinical practice. PATIENTS & METHODS: Cross-sectional and multicenter study performed in atrial fibrillation patients ≥75 years treated with oral anticoagulants ≥3 months. RESULTS: 837 patients (83.0 ± 5.0 years; CHA2DS2-VASc 5.0 ± 1.4; HAS-BLED 2.1 ± 0.9; 70.8% vitamin K antagonists; 29.2% direct oral anticoagulants [DOACs]) were included. Poor adherence was observed in 27.9% of patients. Higher scores in the Pfeiffer's test and FRAIL scale were associated with poorer adherence. Among patients treated with DOACs, 62.3% received the lower doses. Having high CHADS2 score and being older were associated with the use of low doses. CONCLUSION: 28% of patients had a poor adherence to anticoagulant treatment. 62% of patients were treated with the lower doses of DOACs.