In Vitro and In Vivo Performance of Pickering Emulsion-Based Powders of Omega-3 Polyunsaturated Fatty Acids.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) are essential nutrients for human health and have been linked to a variety of health benefits, including reducing the risk of cardiovascular diseases. In this paper, a spray-dried powder formulation based on Pickering emulsions stabilized with cellulose nanocrystals (CNC) and hydroxypropyl methylcellulose (HPMC) has been developed. The formulation was compared in vitro and in vivo to reference emulsions (conventional Self-Emulsifying Drug Delivery System, SEDDS) to formulate n-3 PUFA pharmaceutical products, specifically in free fatty acid form. The results of in vivo studies performed in fasted dogs showed that Pickering emulsions reconstituted from powders are freely available (fast absorption) with a similar level of bioavailability as reference emulsions. In the studies performed with dogs in the fed state, the higher bioavailability combined with slower absorption observed for the Pickering emulsion, compared to the reference, was proposed to be the result of the protection of the n-3 PUFAs (in free fatty acid form) against oxidation in the stomach by the solid particles stabilizing the emulsion. This observation was supported by promising results from short-term studies of chemical stability of powders with n-3 PUFA loads as high as 0.8 g oil/g powder that easily regain the original emulsion drop sizes upon reconstitution. The present work has shown that Pickering emulsions may offer a promising strategy for improving the bioavailability and stability as well as providing an opportunity to produce environmentally friendly (surfactant free) and patient-acceptable solid oral dosage forms of n-3 PUFA in the free fatty acid form.

Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers.

The attractive colloidal and physicochemical properties of cellulose nanofibers (CNFs) at interfaces have recently been exploited in the facile production of a number of environmentally benign materials, e.g. foams, emulsions, and capsules. Herein, these unique properties are exploited in a new type of CNF-stabilized perfluoropentane droplets produced via a straightforward and simple mixing protocol. Droplets with a comparatively narrow size distribution (ca. 1-5 µm in diameter) were fabricated, and their potential in the acoustic droplet vaporization process was evaluated. For this, the particle-stabilized droplets were assessed in three independent experimental examinations, namely temperature, acoustic, and ultrasonic standing wave tests. During the acoustic droplet vaporization (ADV) process, droplets were converted to gas-filled microbubbles, offering enhanced visualization by ultrasound. The acoustic pressure threshold of about 0.62 MPa was identified for the cellulose-stabilized droplets. A phase transition temperature of about 22 °C was observed, at which a significant fraction of larger droplets (above ca. 3 µm in diameter) were converted into bubbles, whereas a large part of the population of smaller droplets were stable up to higher temperatures (temperatures up to 45 °C tested). Moreover, under ultrasound standing wave conditions, droplets were relocated to antinodes demonstrating the behavior associated with the negative contrast particles. The combined results make the CNF-stabilized droplets interesting in cell-droplet interaction experiments and ultrasound imaging.

Solid cellulose nanofiber based foams - Towards facile design of sustained drug delivery systems.

Control of drug action through formulation is a vital and very challenging topic within pharmaceutical sciences. Cellulose nanofibers (CNF) are an excipient candidate in pharmaceutical formulations that could be used to easily optimize drug delivery rates. CNF has interesting physico-chemical properties that, when combined with surfactants, can be used to create very stable air bubbles and dry foams. Utilizing this inherent property, it is possible to modify the release kinetics of the model drug riboflavin in a facile way. Wet foams were prepared using cationic CNF and a pharmaceutically acceptable surfactant (lauric acid sodium salt). The drug was suspended in the wet-stable foams followed by a drying step to obtain dry foams. Flexible cellular solid materials of different thicknesses, shapes and drug loadings (up to 50wt%) could successfully be prepared. The drug was released from the solid foams in a diffusion-controlled, sustained manner due to the presence of intact air bubbles which imparted a tortuous diffusion path. The diffusion coefficient was assessed using Franz cells and shown to be more than one order of magnitude smaller for the cellular solids compared to the bubble-free films in the wet state. By changing the dimensions of dry foams while keeping drug load and total weight constant, the drug release kinetics could be modified, e.g. a rectangular box-shaped foam of 8mm thickness released only 59% of the drug after 24h whereas a thinner foam sample (0.6mm) released 78% of its drug content within 8h. In comparison, the drug release from films (0.009mm, with the same total mass and an outer surface area comparable to the thinner foam) was much faster, amounting to 72% of the drug within 1h. The entrapped air bubbles in the foam also induced positive buoyancy, which is interesting from the perspective of gastroretentive drug-delivery.

Mechanisms behind the stabilizing action of cellulose nanofibrils in wet-stable cellulose foams.

The principal purpose of the investigation was to clarify the mechanisms behind the stabilizing action of cellulose nanofibrils (CNFs) in wet-stable cellulose foams. Following the basic theories for particle-stabilized foams, the investigation was focused on how the surface energy of the stabilizing CNF particles, their aspect ratio and charge density, and the concentration of CNF particles at the air-water interface affect the foam stability and the mechanical properties of a particle-stabilized air-liquid interface. The foam stability was evaluated from how the foam height changed over time, and the mechanical properties of the interface were evaluated as the complex viscoelastic modulus of the interface using the pendant drop method. The most important results and conclusions are that CNFs can be used as stabilizing particles for aqueous foams already at a concentration as low as 5 g/L. The major reasons for this were the small dimensions of the CNF and their high aspect ratio, which is important for gel-formation and the complex viscoelastic modulus of the particle-filled air-water interface. The influence of the aspect ratio was also demonstrated by a much higher foam stability of foams stabilized with CNFs than of foams stabilized by cellulose nanocrystals (CNC) with the same chemical composition. The charge density of the CNFs affects the level of liberation within larger aggregates and hence also the number of contact points at the interface and the gel formation and complex viscoelastic modulus of the air-water interface. The charges also result in a disjoining pressure related to the long-range repulsive electrostatic pressure between particle-stabilized bubbles and hence contribute to foam stability.

Formation of a liquid crystalline phase from phosphatidylcholine at the oil-aqueous interface.

Adsorption of phospholipid (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) and formation of a surface phase at the oil-water interface has been followed by using ellipsometry. The properties of the interfacial phase were found to depend strongly on whether phospholipid was added to the oil phase or to the aqueous phase as liposomal structures. In the latter case a monolayer formed, while if the phospholipid was supplied from the oil phase a lamellar phase appeared at the interface. The effect on the stabilizing surface phase of a surface-active protein (beta-lactoglobulin) was also investigated. The observations are important for understanding stabilizing properties of surface-active compounds commonly used to stabilize emulsions. In addition it has been demonstrated that ellipsometry can be used to study the initial process when a two-phase system consisting of a water and an oil phase is transformed into a three phase system or eventually to a one-phase system.

Ellipsometry studies of nonionic surfactant adsorption at the oil--water interface.

In the presented study we have developed and implemented a methodology for ellipsometry measurements at liquid interfaces that makes it possible to determine the amount adsorbed without assumptions of refractive index or thickness of the adsorbed layer. It was demonstrated that this is possible by combined measurements from different aqueous phases, H(2)O and D(2)O, which were shown to have sufficiently different refractive indices. The methodology was tested by studying adsorption of two types of nonionic poly(ethylene glycol) alkyl ether surfactants, C(n)H(2)(n)(+1)(OC(2)H(4))(m)OH or C(n)E(m) at the decane--aqueous interface, where C(12)E(5) was adsorbed from the oil phase and C(18)E(50) from the aqueous phase. The observed plateau values of the adsorbed amounts were 1.38 and 0.93 mg/m(2) for C(12)E(5) and C(18)E(50), respectively, which is in agreement with the corresponding values of 1.49 and 1.15 mg/m(2) obtained from applying the Gibbs equation to interfacial tension data for the same systems. We will briefly discuss the adsorption behavior in relation to the molecular structure of the surfactant and the phase behavior of the oil--surfactant--aqueous systems in relation to our experimental results.