Invert and double emulsions as a base for microheterogeneous matrices for transdermal delivery of lipophilic drugs

Stable invert emulsions water/oil and double emulsions oil₁/water/oil₂ containing polyisobuthylene as pressure-sensitive polymeric adhesive are prepared. The dispersed phase of the invert emulsions contained micelles of the surfactant Tween 80 (Tw) with solubilized drug (Felodipine) and a skin permeation enhancer (glycerol monooleate, GMO). The active components (Felodipine and GMO) of the double emulsions were incorporated into the internal dispersed phase, while the intermediate water layer contained Tw and hydroxypropylcellulose. Ultradispersed polymer films with good adhesion to skin were prepared from both types of emulsions. The films based on double emulsions demonstrate the ability to release Felodipine at therapeutically effective levels and maintain these levels during the first 24 h to attain a therapeutically required dose. The invert and double emulsions were for the first time utilized as bases for microheterogeneous matrices for delivery of a lipophilic drug in bioavailable form.     

Stability of oil/water (ethanol,lysozyme or lysine) emulsions

Emulsions of n-tetradecane in water (0.1%^v/_^V) homogenized by ultrasounds (1 5 min) were stabilized by 0.5 or 1.0 M ethanol and in the presence of lysozyme (4 mg 100 ml⁻¹) or 1 mM lysine monohydrochloride (14.6 mg 100 ml⁻¹). The zeta potentials and multimodal size distributions of the droplets after 5, 15, 30, 60, 120 min, and 1 and 2 days were determined by dynamic light scattering technique using ZetaPlus apparatus (Brookhaven Instr., USA). Both parameters were determined on the same sample subsequently without any mixing. The effect of pH [4, 6.8 (natural), and 11] was also investigated. The most stable emulsions in 1 M ethanol solutions alone were at pH 6.8 and 11 (the effective diameter D_eff and 350 nm, respectively), while in 0.5 M at pH 4 (D_eff nm). The most stable emulsions with lysozyme were obtained at pH 4 and 1 M ethanol (D_eff nm), and with lysine at pH 6.8 and 0.5 M ethanol (D_eff nm). Except for the emulsions with lysozyme at pH 4 and 6.8, in the rest systems the zeta potentials were negative and ranged between −5 and −85 mV as a function of time and pH. The changes of zeta potential indicate that H⁺ ions are not much potential determining, while OH⁻ ions increase the negative zeta potentials. However, H⁺ ions affect functional groups of lysozyme molecules adsorbed on the alkane droplet, what appears in essential changes of zeta potential and even reversed sign of it in some systems. The results point that stability of these emulsions may also be determined by hydrogen bonding.     

Characterization of silicone oil emulsions stabilized by TiO2 suspensions pre-adsorbed SDS

To study the effects of pre-adsorbed emulsifier on Pickering emulsion stability, the preparation of silicone oil emulsions by TiO₂ suspensions pre-adsorbed sodium dodecyl sulfate (SDS) at the fixed TiO₂ concentration of 0.15 g was carried out below a fiftieth of critical micelle concentration (cmc) of SDS, where all added amounts of SDS are adsorbed on the TiO₂ particles. The stability of the Pickering emulsions incorporating TiO₂ suspensions pre-adsorbed SDS was investigated by measuring the volume fraction of emulsified silicone oil, adsorbed amounts of TiO₂ suspensions pre-adsorbed SDS, oil droplet size, and some rheological responses such as the stress-strain sweep curve and strain and frequency dependences of dynamic viscoelastic moduli. The silicone oil was almost emulsified by TiO₂ suspensions pre-adsorbed SDS above cmc/10³. Increasing in the adsorbed amount of SDS on the TiO₂ particles leads to an increase in the adsorbed amounts of TiO₂ suspensions pre-adsorbed SDS. Such silicone oil emulsions for the first time showed two yield stresses in the stress-strain sweep curve as well as the oscillatory stress-strain curve. The respective yield stresses also increase with an increase in the adsorbed amounts of TiO₂ suspensions pre-adsorbed SDS. From such characteristic rheological properties and a partial sedimentation of some TiO₂ particles remained in the dispersion medium, we proposed the formation of a three dimensional network of the flocculated TiO₂ particles pre-adsorbed SDS on the silicone oil droplets.     

Release of electrolytes from W/O/W double emulsions stabilized by a soluble complex of modified pectin and whey protein isolate

W/O/W double emulsions (DEs) stabilized by charged soluble complexes of whey protein isolate (WPI) and modified pectins were investigated in relation to their stability and the release of two types of electrolytes, NaCl and sodium ascorbate.WPI alone cannot properly stabilize the DEs. The droplet size is relatively large (100 μm) and increases with time. However, addition of modified pectin to form a soluble complex with WPI significantly improved the stability.DEs prepared with two types of oils (medium chain triglycerides (MCT) and R(+)-limonene) were studied by measuring droplet size, creaming, viscosity, and electrolyte release. Irrespective of their very different oil phase nature, both emulsions were stable against coalescence, but R(+)-limonene formed smaller droplets (25 μm) than MCT (35 μm). The electrolyte release rate was significantly higher from the R(+)-limonene that formed DEs with much lower viscosity. R(+)-limonene-DE released 75% of the NaCl after 28 days, while MCT-DE released only 50%. NaCl was released more slowly than sodium ascorbate.Apparently, the release mechanism from R(+)-limonene-DE was found to be “thinning the outer interface and release of the entire inner droplets” while it seems that the release from MCT-DE was slower and “diffusion controlled”.DEs stabilized by WPI/C63 released 12% of the sodium ascorbate after 1 day in milk and remained stable for at least 8 days. However, DEs stabilized with only WPI released about 50% of the sodium ascorbate after 1 day, and phase separated after 8 days.     

The Stability of Highly Concentrated Water-in-Oil Emulsions and Structure of Highly Porous Polystyrene Produced from Them

The porosity of polymer materials produced by polymerizing dispersion media of highly concentrated emulsions may be predicted, provided that the emulsions are stable. The study of the stability of water-in-oil (W/O) emulsions containing styrene as a dispersion medium at 25 and 65°C has shown that emulsions with a dispersed phase fraction of 0.75 and sorbitan monooleate concentrations of 1.5–20.0 vol % are stable to coalescence but are unstable to sedimentation. Emulsions with a dispersed phase fraction of 0.95 are stable to both coalescence and sedimentation at sorbitan monooleate concentrations of 10–20 vol %. Open-pore polymer materials are formed from emulsions with dispersed phase fractions of 0.75 and 0.95 at sorbitan monooleate concentrations of 2.0–3.5 and 10–12 vol %, respectively. At a dispersed phase fraction of 0.75 and a sorbitan monooleate concentration of <2 vol %, a multiple O/W/O emulsion is formed, the polymerization of which yields a porous polymer material containing spherical polystyrene particles inside pores. At higher surfactant concentrations in emulsions with dispersed phase fractions of 0.75 and 0.95 partly destroyed porous materials are formed.     

聚氨酯/聚丙烯酸酯复合乳液粒子热力学平衡形态预测

以水性聚氨酯分散液为种子采用无皂乳液聚合新技术合成出了具有核壳结构的聚氨酯/聚丙烯酸酯（PU/PA）复合聚合物乳液。采用界面张力简化计算方法计算了聚合物与聚合物之间以及聚合物和水之间的界面张力,通过界面自由能变化最小的热力学判据对合成的复合乳液粒子的热力学平衡形态进行了预测。并利用透射电子显微镜观察和用接触角法测定的膜的表面极性对其进行了证实。结果表明：界面自由能变化的最小判据可以推广到PU/PA 体系,本文给出的界面张力的简化计算方法是可行的。     

Studies on stable aqueous poly(o-toluidine) prepared with the use of a water soluble support polymer,polyacrylamide

Polymerization of o-methylaniline or o-toluidine (OT) was studied in aqueous acidic (HCl) medium with or without the use of the support of a water soluble polymer, polyacrylamide (PAAm). Poly(o- toluidine) (POT) produced with PAAm support was in the form of aqueous solution or dispersion that showed high stability and good processibility. High degree of dispersion or near solubility and storage stability of POT thus prepared are explained on the basis of establishment of hydrogen bonding between segments of POT being formed and the PAAm present in the medium thus resulting in a template effect. Studies by UV-visible spectroscopy and FTIR spectroscopy lend support to this view. POT-PAAm composites commonly show higher thermal stability than POT and the composites show DC-electrical conductivities in the range of 10⁻⁹–10⁻¹ S · cm⁻¹ depending on the POT content. Morphological analysis of the optically clear aqueous POT-PAAm solution by transmission electron microscopy (TEM) shows the presence of large clusters of PAAm-supported near-spherical POT nanoparticles in the aqueous PAAm solution. Scanning electron microscopic (SEM) analysis of isolated POT-PAAm composites shows a cocontinuous phase morphology without any trend of gross phase separation. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3243–3256, 1999     

FRAGRANCE EMULSIONS STABILIZED BY A TRIBLOCK COPOLYMER

The phase diagram was determined of the system a fragrance oil, phenethyl alcohol, a commercial triblock copolymer, PE/L101, and water. The stability of emulsions containing 95 wt% water and various amounts of the fragrance and polymer was investigated both visually and with the aid of an optical microscope. The stability of the two-phase emulsions was explained through the interfacial behavior of the polymer and the density change of the oil phase. Double emulsions were found to form when the oil phase composition is close to that of the L₂ phase with maximum water solubilization.     

Partitioning of para-phenylenediamines in oil-in-water emulsions

A method to measure distribution coefficients (P) of electroactive species in situ in turbid oil-in-water emulsions is demonstrated using four p-phenylenediamines (PPD) in oil-in-aqueous-gelatin emulsions of six oils at 40°C. The PPD examined represent a series in β-X-ethyl substitution (4-amino-3-methyl-N-ethyl-N-(β-X-ethyl)aniline) where X = H (2), OH (3), methylsulfonamide (4), and methoxyethyl (5), respectively, for PPD 2–5. The oils examined include di-n-butyl phthalate (DBP), N,N-diethyldodecanamide (DEDA), 1-octanol (OCA), 1-undecanol (UNA), tri-n-hexyl phosphate (THP), and dodecane (DOD). The rotating platinum disk electrode (RPDE) is used as a voltammetric probe of PPD concentration in the aqueous-gelatin phase of the emulsions. Distribution coefficients in macroscopic aqueous/oil systems are also reported, and are illustrated to correlate linearly with values determined in emulsions. The distribution coefficients (P = C_oilC_aqueus) for the different PPD decrease in the order 2 > 5 > 3 ≈ 4 for each of the six oils. The largest distribution coefficients are obtained with THP, and the smallest are obtained with DOD. The interface appears to play a significant role in modifying solute distribution in emulsions.     

Photodegradation of Caffeic Acid in W/O/W Emulsions in the Absence and in the Presence of TiO2

Caffeic acid, a natural phenol with antioxidant and sunscreen activity, can undergo photooxidation upon UV irradiation. The photodegradation of caffeic acid at different concentrations was assessed in water, at pH 4.0 and 6.0, without and with TiO₂. The study was then carried out on W/O/W emulsions entrapping the phenolic acid either in the inner or in the outer aqueous phase in the absence and in the presence of TiO₂, added in the external phase (pH 6.0 or 7.0). The degradation of caffeic acid followed a pseudo-zero order kinetic with an inverse dependence from its initial concentration; at increasing pH of the medium caffeic acid degraded faster. The addition of TiO₂ increased the initial photodegradation rate. Compared with water, W/O/W emulsions protected the phenol towards both the photodegradation and the photocatalytic activity of TiO₂. Multiple systems allowed to incorporate caffeic acid and TiO₂ in the same formulation avoiding any catalytic interactions.     

Preparation and characterization of W/O/W double emulsions containing MgCl2

The aim of present study is to design food-grade W/O/W double emulsions encapsulating Mg²⁺ and investigate their stability and release properties. Prepared emulsions were characterized in terms of global stability, particle size, rheological properties, and interfacial tension. The double emulsions were sensitive to the presence of magnesium salt. The mean droplet size and viscosity of emulsions was positively correlated to MgCl₂ concentration. The microscopic pictures confirmed that the water transfer between two aqueous phases caused the reduced stability of double emulsions. It was suggested that swelling breakdown was the main mechanism in controlling the release of encapsulated Mg²⁺.     

Optimization of Oil-in-Water Emulsion Stability: Experimental Design,Multiple Light Scattering,and Acoustic Attenuation Spectroscopy

To find an optimal formulation of oil-in-water (O/W) emulsions (φ_o = 0.05), the effect of emulsifier nature and concentration, agitation speed, emulsifying time, storage temperature and their mutual interactions on the properties and behavior of these dispersions is evaluated by means of an experimental design (Nemrodw software). Long-term emulsion stability is monitored by multiple light scattering (Turbiscan ags) and acoustic attenuation spectroscopy (Ultrasizer). After matching surfactant HLB and oil required HLB, a model giving the Sauter diameter as a function of emulsifier concentration, agitation speed and emulsification time is proposed. The highest stability of C₁₂E₄-stabilized O/W emulsions is observed with 1% emulsifier.     

Highly Concentrated Emulsions: Physicochemical Principles of Formulation

This review deals with the preparation, stability, rheology and different applications of highly concentrated emulsions. These emulsions, which are known as high internal phase ratio emulsions (HIPRE), gel-emulsions, biliquid foams, etc., containing over 90% internal phase by volume, have a swollen micellar (L₁ or L₂) solution of nonionic or ionic surfactants as a continuous phase. These emulsions have the structure of biliquid foams and behave as gels since they present viscoelastic and plastic properties. The functional macroscopic properties of gel-emulsions are dependent on the structural parameters of the microemulsion continuous phase as well as of the interfacial properties (interfacial tension, bending modules, spontaneous curvature) of surfactant monolayers. The depletion interaction between emulsion droplets due to the non-compensated osmotic pressure of micelles is revealed as a main factor, along with surface forces, which determine the aggregative stability and the rheological properties of these emulsions. The effect of electrolyte and surfactant concentration, temperature, as well as other physicochemical parameters on the fiocculation threshold, stability, and yielding properties of highly concentrated emulsions is explained by the effect of these parameters on the critical micelle concentration (CMC) and the aggregation number of surfactants, and, consequently, on the depletion interaction. The thermodynamic theory of adhesion of fluid droplets in micellar solution and the suggested model of elasticity of gel-emulsions permit to explain the effect of mentioned physicochemical parameters on the elasticity modulus, the plastic strength and the linear deformation of these emulsions. A novel mechanism for the spontaneous formation of gel-emulsions by the phase inversion temperature (PIT) route is suggested, allows the selection of ternary systems able to yield these emulsions, and explains how the droplet size can be controlled during the PIT process. An original model for liquid film rupture is also suggested, and allows the prediction of the effect of structural parameters of micellar solutions and the interfacial properties of surfactant monolayers on the stability of gel-emulsions.     

Synthesis and polymerization of o-hexylaniline: Characterization of the corresponding polyaniline

In the field of research on soluble conducting polymers, the poly(o-alkylanilines) are very interesting because we can expect them to give more soluble polymers and new properties. Like poly(o-propylaniline) (POP), which is more soluble than polyaniline (PANi), poly(o-hexylaniline) (POH) appears to be more soluble in organic solvents than POP because of the longer alkyl groups in the 2-position. The higher solubility confers better processability on this new polymer, and because of this solubility, an NMR study in solution became possible.The nitration of hexylbenzene and the reduction of the resulting product to o-hexylaniline were performed according to the literature. The chemical polymerization was easy and it is possible to produce this polymer in large quantities.The polymerization carried out in anhydrous NH₄F, 2.35 HF medium and in 5 M perchloric acid gave a polymer with almost quantitative yield. The electrochemical behaviour of POH displayed faster electron transfers than PANi in organic solvents, depending on the acido-basicity level of the aqueous solutions. Unlike PANi, fractal growth was not observed.     

Preparation of a stable double emulsion (W1/O/W2): role of the interfacial films on the stability of the system

This paper presents new protocols enabling preparation of W1/O/W2 double emulsions: one, using soybean oil as the O phase, that yields edible emulsions with industrial applications, and a second that yields emulsions with a previously unattainable concentration 15% (w/w) of surfactants in the external phase (the 15% target was chosen to meet the typical industry standard). Preparation of a stable W1/O emulsion was found to be critical for the stability of the system as a whole. Of the various low HLB primary surfactants tested, only cethyl dimethicone copolyol (Abil EM90), A-B-A block copolymer (Arlacel P135), and polyglycerol ester of ricinoleic acid (Grinstead PGR-90) yielded a stable W/O emulsion. Investigation of the surface properties of those surfactants using the monolayer technique found two significant similarities: (1) stable, compressible, and reversibly expandable monolayers; and (2) high elasticity and surface potential. The high degree of elasticity of the interfacial film between W1 and O makes it highly resilient under stress; its failure to break contributes to the stability of the emulsion. The high surface potential values observed suggest that the surfactant molecules lie flat at the O/W interfaces. In particular, in the case of PGR-90, the hydroxyl (-OH) groups on the fatty acid chains serve as anchors at the O/W interfaces and are responsible for the high surface potential. The long-term stability of the double emulsion requires a balance between the Laplace and osmotic pressures (between W1 droplets in O and between W1 droplets and the external aqueous phase W2). The presence of a thickener in the outer phase is necessary in order to reach a viscosity ratio (preferably approximately 1) between the W1/O and W2 phases, allowing dispersion of the viscous primary emulsion into the W2 aqueous phase. The thickener, which also serves as a dispersant and consequently prevents phase separation due to its thixotropic properties, must be compatible with the surfactants. Finally, the interactions between the low and high HLB emulsifiers at the O/W2 interface should not destabilize the films. It was observed that such destructive interaction for the system could be prevented by the use of two high HLB surfactants in the outer aqueous phase: an amphoteric surfactant, Betaine, and an anionic surfactant, sodium lauryl ether sulfate. The combination of such pairs of surfactants was found to contribute to the films' stability.     

Interface composition of multiple emulsions: rheology as a probe

We have investigated the dynamic rheological properties of concentrated multiple emulsions to characterize their amphiphile composition at interfaces. Multiple emulsions (W1/O/W2) consist of water droplets (W1) dispersed into oil globules (O), which are redispersed in an external aqueous phase (W2). A small-molecule surfactant and an amphiphilic polymer were used to stabilize the inverse emulsion (W1 in oil globules) and the inverse emulsion (oil globules in W2), respectively. Rheological and interfacial tension measurements show that the polymeric surfactant adsorbed at the globule interface does not migrate to the droplet interfaces through the oil phase. This explains, at least partly, the stability improvement of multiple emulsions as polymeric surfactants are used instead of small-molecule surfactants.     

Structural analysis of <Emphasis Type="Italic">w</Emphasis>/<Emphasis Type="Italic">o</Emphasis>/<Emphasis Type="Italic">w</Emphasis> multiple emulsions by means of DSC

Summary The properties of the inner and the external aqueous phases, were studied in w/o/w multiple emulsions with light microscopic image analysis and differential scanning calorimetry (DSC). The importance of multiple emulsions lies in the presence of these aqueous phases, making them available for sustained, controlled drug delivery systems. Differentiation of these two aqueous phases, studying the effect of manufacturing technology on droplet structure, quantitative determination of phase volumes and any changes occurring during storage are essential when planning w/o/w emulsions. The present study uses microscopic observations combined with DSC measurements in order to identify the formed structure, at developmental stage in case of different components, preparation methods, and stirring rates. These tools are beneficial during manufacturing as in process controls, or to ensure product quality.     

Emulsion approach to production of polymer films used as carriers of lysozyme

A new approach to producing polymer films with an immobilized bactericidal enzyme, lysozyme, is proposed based on oil-in-water emulsions containing nonionic surfactants and hydrophobic and hydrophilic polymers. The rheological properties, stability, dispersity, and film-forming ability of the emulsions are studied. It is established that lysozyme is present in the films in a nanocrystalline form, which ensures its rapid release into aqueous buffer solutions with retaining its enzymatic activity.     

Preparation of highly monodisperse W/O emulsions with hydrophobically modified SPG membranes

Experimental investigations on the hydrophobic modification of SPG membranes and the preparation of monodisperse W/O (water-in-oil) emulsions using the modified membranes were carried out. Effects of the osmotic pressure of disperse phase, the average pore size of membranes, emulsifier concentrations in continuous phase and the transmembrane pressure on the average size, size distribution and size dispersion coefficient of emulsions were systematically studied. The stability of W/O emulsions was also investigated. The results showed that SPG membranes took on excellent hydrophobicity through the modification by silane coupler reagent (octyltriethoxysilane) or by silicone resin (polymethylsilsesquioxane). Monodisperse W/O emulsions with size dispersion coefficient of about 0.25, which meant high monodispersity, were successfully prepared by using the hydrophobically modified SPG membranes with average pore sizes of 1.8, 2.0, 2.5, 4.8 and 11.1 microm. When the osmotic pressure was lower than 0.855 MPa, the average size of emulsions was gradually increased while the size dispersion coefficient delta gradually decreased with the osmotic pressure; when the osmotic pressure was higher than 0.855 MPa, both the coefficients kept unvarying. When kerosene was saturated with disperse phase in advance, the average size of emulsions became larger and the monodispersity of emulsions was slightly better than that prepared using unsaturated kerosene. The smaller the pore size of SPG membranes was, the better the monodispersity of the W/O emulsions. The average size and size dispersion coefficient delta were nearly independent on the emulsifier concentrations when the PGPR concentration was in the range from 0.5 to 5.0 wt%, whereas both of them slightly increased as the PGPR concentration was below 0.5 wt%. The effect of the transmembrane pressure on size distributions was slight. Both the average size and size dispersion coefficient delta slightly increased to some extent with the increase of the transmembrane pressure in the experimental range. The stability of the W/O emulsions was dependent on the storage time. The mean size of W/O emulsions decreased gradually with the increase of storage time at the first 35 days, and then kept constant; while the size dispersion coefficient of W/O emulsions was nearly not changed.     

Controlled/living heterogeneous radical polymerization in supercritical carbon dioxide

Supercritical carbon dioxide (scCO₂) is an inexpensive and environmentally friendly medium for radical polymerizations. ScCO₂ is suited for heterogeneous controlled/living radical polymerizations (CLRPs), since the monomer, initiator, and control reagents (nitroxide, etc.) are soluble, but the polymer formed is insoluble beyond a critical degree of polymerization (J_crit). The precipitated polymer can continue growing in (only) the particle phase giving living polymer of controlled well‐defined microstructure. The addition of a colloidal stabilizer gives a dispersion polymerization with well‐defined colloidal particles being formed. In recent years, nitroxide‐mediated polymerization (NMP), atom transfer radical polymerization (ATRP), and reversible addition fragmentation chain transfer (RAFT) polymerization have all been conducted as heterogeneous polymerizations in scCO₂. This Highlight reviews this recent body of work, and describes the unique characteristics of scCO₂ that allows composite particle formation of unique morphology to be achieved. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 3711–3728, 2009