Feeding liquid, non-ionic surfactant and cyclodextrin affect the properties of insulin-loaded poly(lactide-co-glycolide) microspheres prepared by spray-drying.

The potential of spray-drying technique for the encapsulation in poly(lactide-co-glycolide) (PLGA) microspheres of bovine insulin, a poorly stable peptide, has been investigated. Insulin-loaded microspheres were prepared by spray-drying different feeding liquids containing insulin and PLGA, that is a S/O dispersion, a W/O emulsion or an acetic acid solution. In the case of the emulsion, insulin was also co-encapsulated with either non-ionic surfactants such as polysorbate 20 and poloxamer 188, or complexing agents such as HPbetaCD. In the microspheres prepared from the acetic acid solution of insulin and PLGA, HPbetaCD was tested. Microspheres containing surfactants were aggregated, whereas good quality particles displaying a mean diameter in the range 12.1-27.9 microm were produced in the other cases. Insulin was efficiently loaded inside microspheres except for S/O formulation (only 22% of total insulin content was entrapped). The impact of the microencapsulation process on insulin chemical and conformational stability was assessed by HPLC, circular dichroism and turbidimetry studies. Under the adopted manufacture conditions, insulin was encapsulated in the native state and its chemical and conformational stability was preserved along the fabrication process. The formulations containing only insulin displayed low burst effects (6-11%), whereas the addition of surfactants resulted in much higher burst effects (49-54%) and faster release rate. The co-encapsulation of HPbetaCD slowed down the overall release rate and, in the case of microspheres prepared from the emulsion, allowed a constant insulin release up to 45 days. The study of insulin stability along the release phase showed that insulin was released in the intact form and un-released insulin was stable inside all the microsphere formulations. We conclude that insulin can be effectively encapsulated in PLGA microspheres by the spray-drying technique. Additives with complexing properties such as HPbetaCD have demonstrated a potential in optimizing the release rate of insulin when used in microspheres prepared from W/O emulsions.     

Formulation of shear rate sensitive multiple emulsions.

This work mainly concentrates on the formulation of W/O/W multiple emulsions capable of breaking and releasing their inner aqueous phase under shear rates compatible with agroalimentary, pharmaceutical and cosmetic applications. Three kinds of multiple emulsions were studied: one with a high concentration of primary emulsion, not viscosified in the external aqueous phase; multiple emulsions gelified with a synthetic polymer (Carbopol 974P((R))); and other multiple emulsions thickened with chemically modified cellulose (hydroxypropylcellulose). The results of this study show the influence of the composition of the external aqueous phase of the emulsions on their fragmentation and release as a function of the shear rate. Despite these differences of behavior with respect to the shear rate, each emulsion fits to Taylor's theoretical framework, indicating that the bursting mechanisms of the globules under shear are the same whatever the composition of the multiple emulsions.     

Hydrolysis of the oil phase of a W/O/W emulsion by pancreatic lipase.

W/O/W emulsions are expected to protect bioactive substances from degradation by pancreatic enzymes. We investigated the enzymatic hydrolysis of the oil phase and release of a marker substance from the inner-aqueous phase to the outer-aqueous phase using an artificial digestive fluid. Octanoic acid triacylglycerol (C8TG) was used as the oil phase. W/O/W emulsions were prepared by two-step homogenization and succeeding membrane filtration. When the artificial digestive fluid containing lipase and gall was added to the emulsion, release of the marker substance from the inner-phase solution, oil-phase hydrolysis, and emulsion coalescence occurred in that order. When a coarse emulsion and 0.2- and 0.8-microm membrane-filtered fine emulsions were treated with the fluid for 1 h, the degrees of C8TG hydrolysis were 3.8%, 55% and 57%, the fractions of the marker substance released from the inner-water phase were 2.7%, 89% and 72%, and the median diameters of the oil droplets were changed from 32 to 23 microm, 0.71 to 27 microm, and from 2.2 to 26 microm, respectively. These results suggested that the diameter of the oil droplets in the W/O/W emulsion significantly affected the release profile of the marker loaded in the inner-water phase of the emulsion.     

Size of lipid microdroplets effects results of hepatic arterial chemotherapy with an anticancer agent in water-in-oil-in-water emulsion to hepatocellular carcinoma

We have initially prepared a new drug delivery system for hepatocellular carcinoma (HCC). Using sonication and a detergent, iodinated poppy seed oil (IPSO) can be mixed with an aqueous solution of epirubicin to make a water-in-oil emulsion. The water-in-oil emulsion is further passed through a microporous glass membrane and split into saline to make a long-term inseparable water-in-oil-in-water emulsion (W/O/W) that consists of IPSO microdroplets. To investigate the effect of the size of IPSO microdroplets on the efficacy of injection chemotherapy with W/O/W in patients with HCC, 32 HCC patients were randomly assigned and treated with W/O/W of small IPSO microdroplets (30 micrometers in diameter) containing 60 mg of epirubicin (n = 16, group A) or W/O/W of large IPSO microdroplets (70 micrometers) containing the same amounts of epirubicin (n = 16, group B). Effects were assessed by measuring the percentage of decline of the alpha-fetoprotein (AFP) level in a week from the AFP level immediately before the treatment. The decline was significantly larger in group B (50.5 +/- 19.8, mean +/- S.D.) compared with group A (18.9 +/- 33.1; p <.005). The size of IPSO microdroplets injected into the hepatic artery determines the decrease of serum AFP levels of the patients with HCC.     

Formulation optimization of water-in-oil-water multiple emulsion for intestinal insulin delivery.

Formulation optimization of the water-in-oil-in-water multiple emulsion incorporating insulin was performed based on statistical methods such as the orthogonal experimental design and the response surface evaluation. As model formulations, 16 types of emulsions were prepared according to the orthogonal experimental design. To optimize the formulation, the influence of causal factors such as amounts of gelatin, insulin, oleic acid (OA) and the volume ratio of the outer aqueous phase to total and agitation time of the second emulsification process on individual characteristics of the emulsion, such as inner droplet size, viscosity, stability and pharmacological effect, was evaluated first. Based on the analysis of ANOVA, it was concluded that the droplet size of the emulsion was influenced by the volume ratio of the outer aqueous phase significantly. The viscosity of the emulsion was affected by these causal factors and their interactions; however, the most predominant contribution of all causal factors was the volume ratio of the outer aqueous phase. Similarly, one of the most important characteristics in the design of the formulation, stability, was affected by the causal factors. With regard to the hypoglycemic effect, the most influential factor was the content of OA in the emulsion. By means of a novel optimization technique involving a multivariate spline interpolation (MSI), formulation optimization was performed with respect to pharmacological effect and stability, and the optimum formulation with a desirable pharmacological effect and high stability was successfully estimated.     

Optimization of a thermally reversible W/O/W multiple emulsion for shear-induced drug release.

PURPOSE: The present work aimed at improvement of the formulation of a previously developed thermo-reversible W/O/W multiple emulsion by increasing the emulsion stability and reaching a higher fraction of an encapsulated drug released under shear. The emulsion was based on high molecular weight graft-copolymers of poly(acrylic acid) and Pluronic F127 as stabilizing agents. METHODS: Once a stable W/O/W thermo-reversible multiple emulsion was obtained via a fine-tuning of the formulation, rheological, granulometric and conductometric tests were performed to assess the thermo-reversible behavior and the fragmentation-release characteristics of the new W/O/W multiple emulsion. RESULTS: The emulsion exhibited a 10(3) fold increase in viscosity over a range of temperatures from 20 to 40 degrees C. At moderate shearing, a complete release of the marker encapsulated in the internal aqueous phase was observed (99.6%) at 35 degrees C, whereas only 30% was released at 20 degrees C. Under similar conditions at 35 degrees C, slightly more than 50% was released for the initial formula. CONCLUSION: Additionally, the ease of fabrication of the thermo-reversible W/O/W multiple emulsion combined with the complete release under shear at body temperature and the superior emulsion stability suggest numerous applications in the controlled release of drugs.     

Optimisation of bacterial release from a stable microfluidic-generated water-in-oil-in-water emulsion

Application of droplet microfluidics for the encapsulation of bacteria in water-in-oil-in-water (W/O/W) emulsion allows for production of monodisperse droplets with controllable size. In this study the release of bacteria from W/O/W emulsion, the effect of the double emulsion structure on bacterial growth and metabolic activity, and the stability and mechanism of bacterial release were investigated. W/O/W emulsions were formed using a double flow-focusing junction microfluidic device under controlled pressure to produce droplets of approximately 100 μm in diameter containing an inner aqueous phase (W₁) of about 40–50 μm in diameter. GFP-labelled Escherichia coli (E. coli-GFP) bacteria were encapsulated within the W₁ droplets and the stability of emulsions was studied by monitoring droplet size and creaming behaviour. The double emulsions were stabilised using a hydrophilic (Tween 80) and a lipophilic surfactant (polyglycerol polyricinoleate) and were destabilised by altering the osmotic balance, adding NaCl either in the inner W₁ phase (hypo-osmotic) or outer W₂ phase (hyper-osmotic). The release of E. coli-GFP was monitored by plating on agar whereby the colony form unit (CFU) of the released bacteria was determined while fluorescent microscopy was employed to observe the mechanism of release from the droplets. The release of E. coli-GFP was significantly increased with higher concentrations of NaCl and lower amounts of Tween 80. Microscopic observation revealed a two-step mechanism for the release of bacteria: double W/O/W emulsion droplet splitting to release W₁ droplets forming a secondary double emulsion followed by the collapse of W₁ droplets to release E. coli-GFP into the continuous aqueous phase.

Encapsulation enhanced viability and metabolic activity. Nutrients can cross the oil layer. Bacterial release increased while emulsion stability decreased at high osmotic pressure and low surfactant concentration. Two-step release mechanism observed.     

Protein encapsulation into biodegradable microspheres by a novel S/O/W emulsion method using poly(ethylene glycol) as a protein micronization adjuvant.

A new method for preparing protein-loaded biodegradable microspheres by a process involving solid-in-oil-in-water (S/O/W) emulsion was established using poly(ethylene glycol) (PEG). In the first step, a protein solution was lyophilized with PEG, which resulted in the formation of spherical protein microparticles, less than 5 microm in diameter, dispersed in a continuous PEG phase. This process was well explained by the aqueous phase separation phenomenon induced by freezing-condensation. Since this lyophilizate could be directly dispersed in an organic phase containing biodegradable polymer by dissolving PEG with methylene chloride, a conventional in-water drying method could be adopted in the second step. Through this S/O/W emulsion process, horseradish peroxidase was effectively entrapped into monolithic-type microspheres of poly(DL-lactic-co-glycolic acid) (PLGA), without significant loss of activity. Bovine superoxide dismutase (bSOD), as another model protein, could be encapsulated into reservoir-type microspheres by the 'polymer-alloys method' using both poly(DL-lactic acid) (PLA) and PLGA. The initial release of bSOD from this reservoir-type microsphere was efficiently reduced. Further, the bSOD release kinetics could be suitably modified by adjusting the loading amounts of PEG or polymer composition. In this study, the multi-functional nature of PEG was successfully utilized in the preparation and designing of protein-loaded microspheres.     

Oral multiple w/o/w emulsion formulation of a peptide salmon calcitonin: in vitro-in vivo evaluation

BACKGROUND: Salmon calcitonin (sCT) is a polypeptide hormone consisting of 32 amino acid residues (MW approx. 3400 Da), which can be used successfully for the treatment of osteoporosis, Paget's disease and hypercalcaemia. Only nasal and parenteral preparations of sCT are currently available, and as injections are poorly accepted by patients, nonparenteral preparations for oral, rectal and nasal administration are highly desirable. However, oral sCT is poorly bioavailable, being susceptible to enzymatic degradation in the gastrointestinal tract. OBJECTIVES: To design a formulation of sCT suitable for oral use. METHOD: A water/oil/water (w/o/w) type multiple emulsion formulation was designed for oral application of sCT. sCT was placed in the inner water phase, and a protease inhibitor, aprotinin, was included in the outer water phase of this system to investigate the influence of protease inhibitors in the presence of sCT. The effectiveness of the formulation was evaluated in vitro by placing emulsion samples in a dialysis medium and in vivo by using a rat model. RESULTS: Incorporating sCT in the inner aqueous phase of a w/o/w emulsion appears to protect the peptide from enzymatic degradation. sCT was further protected by incorporating the protease inhibitor, aprotinin, in the outer aqueous phase. CONCLUSION: w/o/w emulsion formulations appear to be promising carrier systems for peptide-protein drugs.     

Preparation, structure and release profile of polypeptide microcapsules

Three types of block polypeptide, [Lys(Z)]_m(Sar)_n, [Glu(OMe)]_m(Sar)_n, and (Ala)_m(Sar)_n, were synthesized and used for preparation of polypeptide microcapsules. The (Sar)_n segment improved solubility of the polypeptides in chloroform, and enabled preparation of peptide microcapsules by a solvent-evaporation technique of W/O/W emulsion. The size of microcapsules depended on the preparative process of W/O emulsion. The most frequent diameter of microcapsules prepared by sonication of W/O emulsion was ca. 30 μm, while it was ca. 100 μm when prepared by magnetic stirring of W/O emulsion. SEM observation revealed that one microcapsule contained many small capsules inside (microcapsule aggregate). FITC-dextran was encapsulated in the microcapsule, and the release was studied in a buffer solution at 37°C. The release started with a fast release followed by a slow release. This pattern is attributed to the unique structure of microcapsules, in which microcapsule aggregate is enveloped by a larger microcapsule. The release rate was different according to the nature of polypeptides, and it increased in the order of [Lys(Z)]_m(Sar)_n < [Glu(OMe)]_m(Sar)_n < (Ala)_m(Sar)_n. This order is an decreasing solubility of the peptides in chloroform, which was used for preparation of W/O/W emulsion. The higher the solubility of polypeptide in chloroform, the less porous the microcapsule wall would be.     

Insulin-loaded biodegradable PLGA microcapsules: initial burst release controlled by hydrophilic additives.

We investigated the controlled release of human insulin at an initial stage from poly(DL-lactic-co-glycolic acid) (PLGA, M(w) 6600) spherical matrices. PLGA microcapsules were prepared by the novel solvent evaporation multiple emulsion process. When the crystalline insulin was dispersed in dichloromethane as solid-in-oil (S/O) dispersion, it was found that most of insulin molecules were inlaid on the surface of PLGA microcapsules. Consequently, insulin-loaded PLGA microcapsules exhibited marked rapid release of insulin within several hours in both in vivo and in vitro experiments. On the other hand, the addition of glycerol or water in the primary dichloromethane dispersion results in drastically suppressed initial release. It was found by SEM observation that water- or glycerol-in-oil (W/O or G/O) type mini-emulsion droplets with a mean diameter of 300-500 nm were formed in this primary solution. This phenomenon can be theoretically presumed to occur because insulin and PLGA molecules, having amphiphilic properties, converge on the interface between the hydrophilic additive and dichloromethane. Hence, insulin molecules heterogeneously located in the inside of PLGA microcapsules, not on the surface, would be gradually released with PLGA hydrolytic decomposition. As an additional effect of glycerol, the initial burst was further suppressed due to the decrease of the glass transition temperature of PLGA from 42.5 to 36.7 degrees C. Since the annealing of PLGA molecules took place at around 37 degrees C, the porous structure of microspheres immediately disappeared after immersion in PBS or subcutaneous administration. The insulin diffusion through the water-filled pores would be effectively prevented. The strict controlled initial release of insulin from the PLGA microsphere suggested the possibility of utilization in insulin therapy for type I diabetic patients who need construction of a basal insulin profile.     

Drug release from w/o/w emulsions prepared with different chitosan salts and concomitant creaming up.

Water-in-oil-in-water (w/o/w) emulsions containing chitosan and tryptophan in the inner aqueous phase were prepared. The acids used to dissolve chitosan were formic, acetic, butyric and lactic acids. The effects of these organic acids and pH of the inner aqueous phase on the release of tryptophan and on the separation of the aqueous phase due mainly to creaming up during storage were studied. When the inner aqueous phase was an acidic chitosan solution, the release rate was almost the same irrespective of the acids mentioned above. When acetic and butyric acids were neutralized with sodium hydroxide, the release of tryptophan was prolonged. However, it was enhanced again by an excess amount of sodium hydroxide. On the other hand, the release was enhanced after neutralization of formic and lactic acids. Separation of the aqueous phase from the w/o/w emulsion during storage was remarkably delayed after neutralizing the chitosan solution containing acetic or butyric acids, while not so much in the cases of formic and lactic acids. It is concluded that these w/o/w emulsions were stabilized in the presence of neutralized chitosan gel suspensions containing acetate or butyrate ions in the inner aqueous phase.     

How cyclodextrin incorporation affects the properties of protein-loaded PLGA-based microspheres: the case of insulin/hydroxypropyl-beta-cyclodextrin system.

The aim of this work was to study the influence of cyclodextrin (CD) incorporation on the properties of protein-loaded poly(lactide-co-glycolide) (PLGA) microspheres, with particular regards to protein release kinetics. To this purpose, insulin-loaded microspheres were prepared by spray-drying emulsion or solution formulations, with or without hydroxypropyl-beta-cyclodextrin (HPbetaCD), and fully characterized for encapsulation efficiency and release kinetics of both insulin and cyclodextrin. Homogeneous populations of spherical microparticles entrapping both insulin and HPbetaCD were obtained. In order to get an insight into insulin/HPbetaCD interactions occurring inside microspheres, Fourier transform infrared (FTIR) analysis in the Amide I region was performed. FTIR spectra of dried microspheres containing HPbetaCD showed a change in insulin secondary structure, attributed to the presence of insulin/HPbetaCD complexes within microspheres. Insulin release was affected by the presence of HPbetaCD depending on the initial formulation conditions. In the case of microspheres prepared from emulsion, cyclodextrin reduced only insulin burst, whereas in the case of microspheres obtained from solution, the overall insulin release rate was slowed down. Combining the release kinetics of HPbetaCD with the FTIR results on hydrated microspheres, it was concluded that the formation of insulin/HPbetaCD complexes inside microspheres is critical to decrease protein diffusivity in the polymer matrix and achieve an effective modulation of protein release rate.     

Double emulsions: how does release occur?

Water-in-oil-in-water double emulsions (W/O/W) consist of dispersed oil globules containing smaller aqueous droplets. These materials offer interesting possibilities for the controlled release of chemical species initially entrapped in the internal droplets. A better understanding of the stability conditions and release properties in double emulsions requires the use of model systems with a well-defined droplet size. In this paper, we use quasi-monodisperse double emulsions made of calibrated water droplets and oil globules to investigate the two mechanisms that are responsible for the release of a chemical substance (NaCl). (i) One is due to the coalescence of the thin liquid film separating the internal droplets and the globule surfaces. (ii) The other mechanism termed as 'compositional ripening' occurs without film rupturing; instead it occurs by diffusion and/or permeation of the chemical substance across the oil phase. By varying the proportions and/or the chemical nature of the surface active species it is possible to shift from one mechanism to the other one. We therefore study separately both mechanisms and we establish some basic rules that govern the behavior of W/O/W double emulsions.     

Submicron lipid emulsion as a drug delivery system for nalbuphine and its prodrugs.

This study investigates the submicron lipid emulsion as a potential parenteral drug delivery system for nalbuphine and its ester prodrugs. Submicron emulsions were prepared using egg phospholipid as the main emulsifier, various co-emulsifiers were also incorporated, including Brij 30, Brij 98, and stearylamine. Squalene as the oil phase formed stable emulsions with small particles. Drug release was affected by incorporating various co-emulsifiers and drugs with various lipophilicity. The loading of nalbuphine into lipid emulsions resulted in the slower and sustained release of nalbuphine. Lipid emulsions containing Brij 98 could further enhance the release of prodrugs as compared to the aqueous solution (control) especially for nalbuphine enanthate (NAE). Hemolysis caused by the interaction between erythrocytes and lipid emulsions was investigated. Brij 30 and Brij 98 could shield the hemolytic activity of phospholipids in the oil/water interface, decreasing the acute toxicological potential of the emulsions. The in vivo analgesic activity of various emulsions was examined by a cold ethanol tail-flick test. The analgesic duration and potency were significantly increased by incorporating nalbuphine and NAE into Brij 98-containing emulsions. There was no need for nalbuphine benzoate (NAB) to show a controlled delivery manner by encapsulating into emulsions, since NAB itself could prolong the analgesic duration of nalbuphine due to the slow enzyme degradation. The in vivo analgesic activity correlated well to the profiles of in vivo pharmacokinetic profiles. The study demonstrates the feasibility of using submicron lipid emulsion as the parenteral drug delivery system for nalbuphine and its prodrugs.     

Influence of oil droplet surface charge on the performance of antibody--emulsion conjugates.

Targeted drug delivery requires binding of (and subsequent uptake by) the carrier to target cells. The purpose of our present study is to compare the binding and uptake of emulsions with different electric surface properties to SK-BR3 cell line, which over-expresses the HER2 receptor. Cationic emulsion was prepared by incorporating 0.25% w/w of the cationic lipid, stearylamine in the formulation while the anionic emulsion formulation was identical but lacking stearylamine. Immunoemulsions were prepared by conjugating the 2-iminothiolane derivative of the monoclonal antibody trastuzumab (Herceptin) through the reactive maleimide group of the octadecyl-4-(maleimidomethyl)cyclohexane-carboxylic amide linker which was incorporated in the oil phase of the anionic and cationic emulsions. Cationic emulsion exhibited a droplet size of approximately 130 nm and a zeta potential of +50 mV compared to anionic emulsion with a droplet size of approximately 140 nm and a zeta potential of -30 mV which decreased to -5 mV following antibody coupling. There was no significant difference in the coupling efficiency of trastuzumab to anionic and cationic emulsions which was in the range of 60-70%. The cationic emulsion and immunoemulsion appeared to be physically stable over a long period of time, as indicated by particle-size measurements while the droplets of the anionic immunoemulsion coalesced with time resulting in phase separation within 20 days storage at 4 degrees C. The results of binding and uptake to cells showed that both cationic and anionic immunoemulsions bind and internalized to cells much more than the respective blank emulsions. The enhanced penetration of the probe coumarin-6 with both immunoemulsions clearly indicated that the internalization process was mainly controlled by a cell-receptor endocytosis mechanism mediated by the binding affinity of trastuzumab to the cell surface receptor since the uptake of the cationic immunoemulsion was not significantly different from the uptake of the anionic immunoemulsion. However, only the cationic immunoemulsion might be considered for further investigation in view of its long standing physical stability.     

Preparation and properties of a stable intravenous lorazepam emulsion

Lorazepam is normally administered as a solution in organic solvents such as propylene glycol. This type of formulation is undesirable. This study describes the development of a parenteral emulsion formulation for lorazepam. The stability of lorazepam in the emulsion was examined. Ten per cent corn oil emulsions stabilized with egg lecithin, Pluronic F68 and Pluronic F88 were used. The incorporation of lorazepam does not appear to destabilize the emulsion, and lorazepam itself appears to be stable for at least 1 year in this liquid formulation.
Haemolysis caused by emulsion formulations containing lorazepam and different emulsifiers was evaluated using human and rabbit blood to assess their safety as parenteral drug carriers. The results show that the emulsions did not have any significant haemolytic activity whereas organic solvents and solutions of lorazepam in organic solvents caused substantial haemolysis.     

Oil components modulate physical characteristics and function of the natural oil emulsions as drug or gene delivery system.

Oil-in-water (o/w) type lipid emulsions were formulated by using 18 different natural oils and egg phosphatidylcholine (egg PC) to investigate how emulsion particle size and stability change with different oils. Cottonseed, linseed and evening primrose oils formed emulsions with very large and unstable particles. Squalene, light mineral oil and jojoba bean oil formed stable emulsions with small particles. The remaining natural oils formed moderately stable emulsions. Emulsions with smaller initial particle size were more stable than those with larger particles. The correlation between emulsion size made with different oils and two physical properties of the oils was also investigated. The o/w interfacial tension and particle size of the emulsion were inversely proportional. The effect of viscosity was less pronounced. To study how the oil component in the emulsion modulates the in vitro release characteristics of lipophilic drugs, three different emulsions loaded with two different drugs were prepared. Squalene, soybean oil and linseed oil emulsions represented the most, medium and the least stable systems, respectively. For the lipophilic drugs, release was the slowest from the most stable squalene emulsion, followed by soybean oil and then by linseed oil emulsions. Cationic emulsions were also prepared with the above three different oils as gene carriers. In vitro transfection activity was the highest for the most stable squalene emulsion followed by soybean oil and then by linseed oil emulsions. Even though the in vitro transfection activity of emulsions were lower than the liposome in the absence of serum, the activity of squalene emulsion, for instance, was ca. 30 times higher than that of liposome in the presence of 80% (v/v) serum. In conclusion, the choice of oil component in o/w emulsion is important in formulating emulsion-based drug or gene delivery systems.     

Formulation of re-dispersible dry o/w emulsions using cellulose nanocrystals decorated with metal/metal oxide nanoparticles

This study describes for the first time the preparation of re-dispersible surfactant-free dry eicosane oil emulsion using cellulose nanocrystals (CNCs) using the freeze-drying technique. Surface properties of CNCs constitute a critical point for the stability of o/w emulsions and thus can affect both the droplet size and dispersion properties of the emulsion. Therefore, surface modification of CNCs was performed to understand its effect on the size of the obtained re-dispersible dry o/w eicosane emulsion. Decoration of the CNC surface with metal and metal oxide nanoparticles was conducted through the available alcoholic groups of glycosidic units of CNC, which played a dual role in reducing and stabilizing nanoparticles. Of these nanoparticles, silver (AgNPs), gold (AuNPs), copper oxide (CuO-NPs), and iron oxide (Fe₃O₄-NPs) nanoparticles were prepared via a facile route using alkali activated CNCs. Thorough characterizations pertaining to the as-prepared nanoparticles and their re-dispersible dry eicosane o/w emulsions were investigated using UV-vis spectroscopy, TEM, XRD, particle size, zeta potential, and STEM. Results confirmed the ability of CNCs to stabilize and/or reduce the formed nanoparticles with different sizes and shapes. These nanoparticles showed different shapes and surface charges accompanied by individual morphologies, reflecting on the stability of the re-dispersed dry eicosane emulsions with droplet sizes varying from 1.25 to 0.5 μm.

Schematic diagram for the detailed preparation of dry eicosane o/w emulsions.     

Influence of three synthetic membranes on the release of caffeine from concentrated W/O emulsions.

We measured the release rate characteristics of caffeine from concentrated emulsions using three different sources of synthetic membranes. The formulations tested included, on the one hand, two stable cosmetic concentrated W/O emulsions (90% w/w) - one with a non ionic surfactant and one with a silicone surfactant - and on the other hand, a commercially available hydroalcoholic gel. All formulations contained 5% caffeine. In vitro diffusion measurements (24 h) were performed with static diffusion Franz cells. A silicone membrane could not allow us to differentiate the two concentrated emulsions (CE), but the two other membranes, not rate limiting, showed difference in the release profile of caffeine from the two CE. Results with the cellulose and polysulfone membrane showed that in vitro release of caffeine is influenced by the nature of the emulsifier in the concentrated emulsion, the non ionic surfactant being more efficient than the silicone surfactant. The polysulfone membrane was the only one that allows statistical differentiation of the three products. For further studies the polysulfone membrane will be use to make screening on concentrated emulsions.