Simple Method for Rheological Determination of Surfactant Layer Thickness, Adsorbed on Soft Rubber Particles.

Natural rubber latex is a colloidal suspension of particles, which is very important for many industrial applications. These latex particles are not only polydispersed but also very soft and deformable, which makes the prediction of rheological properties much difficult. Herein, the rheology of natural rubber latex has been studied at high particle concentrations, analyzing the effects of surfactant addition on colloidal stability. A hydrophobically modified inulin surfactant (INUTEC NRA) was selected for this study since previous works had shown that this inulin surfactant imparts good colloidal stability to polystyrene latex particles. The most important objective was studying the influence of the surfactant on the particle adsorbed layer and determining the thickness of the adsorbed surfactant layer. The results showed that the relative viscosity increased as a function of latex volume fraction, and this increase became extremely sharp as the volume fraction approached the maximum packing volume fraction, as expected. This variation in viscosity with the volume fraction has a complex behavior, which could not be analyzed using conventional models based on hard rigid spheres, such as Krieger-Dougherty (K-D) or Maron-Pierce (M-P). Herein, we describe a simple semiempirical method to determine the surfactant adsorbed layer thickness, based on the linear dependence of intrinsic viscosity with 1/(ϕmax - ϕ)2, where ϕ is the volume fraction of rubber particles and ϕmax is the maximum volume fraction at which viscosity tends to infinity. The difference in the maximum packing fraction, with and without the surfactant, allows the calculation of the adsorbed layer thickness, δ ≈ 2.8 nm, which is a good estimate for the thickness of surfactant molecules adsorbed on latex particles. This surfactant thickness has been confirmed by direct measurements using dynamic light scattering (DLS), which gave a value of 3.1 nm. Viscoelastic oscillatory measurements have also been performed, showing that natural rubber particle suspensions are predominantly elastic above ϕ = 0.63 latex volume fractions. The elastic modulus has been analyzed as a function of surfactant concentration, confirming that the stability of latex particles is mainly controlled by the surfactant concentration.

Solubilization of active ingredients of different polarity in Pluronic® micellar solutions - Correlations between solubilizate polarity and solubilization site.

The solubilization of two pharmaceutically active ingredients (AI) with significantly different water solubility, namely carbamazepine and fenofibrate (solubility of 150ppm and 10ppm, respectively), has been investigated using a series of Pluronics® (Poloxamers) containing different ethylene oxide and propylene oxide (EO/PO) units in the molecule. The results show largely enhanced solubilization of fenofibrate by Pluronic® micelles that increases with the PPO chain length provided the temperature is above the critical micelle temperature (cmt). In contrast the more water-soluble carbamazepine only shows a moderate increase in solubilization upon addition of Pluronics®. Small angle neutron scattering (SANS) and pulsed field gradient (PFG) NMR experiments show that the solubilization of fenofibrate occurs in the core of the micelles, whereas carbamazepine shows no direct association with the micelles. These clearly different solubilization mechanisms for the two AIs were confirmed by Nuclear Overhauser Enhancement Spectroscopy (NOESY) experiments, which show that fenofibrate interacts only with the PPO core of the micelle, whereas carbamazepine interacts with both PPO and PEO similarly. Accordingly, the large enhancement of the solubilization of fenofibrate is related to the fact that it is solubilized within the PPO core of the Pluronic® micelles, while the much more moderate increase of carbamazepine solubility is attributed to the change of solvent quality due to the presence of the amphiphilic copolymer and the interaction with the EO and PO units in solution.

Assessment of formulation robustness for nano-crystalline suspensions using failure mode analysis or derisking approach.

The small particle size of nano-crystalline suspensions can be responsible for their physical instability during drug product preparation (downstream processing), storage and administration. For that purpose, the commercial formulation needs to be sufficiently robust to various triggering conditions, such as ionic strength, shear rate, wetting/dispersing agent desorption by dilution, temperature and pH variation. In our previous work we described a systematic approach to select the suitable wetting/dispersant agent for the stabilization of nano-crystalline suspension. In this paper, we described the assessment of the formulation robustness (stabilized using a mixture of sodium dodecyl sulfate (SDS) and polyvinylpyrrolidone (PVP) and) by measuring the rate of perikinetic (diffusion-controlled) and orthokinetic (shear-induced) aggregation as a function of ionic strength, temperature, pH and dilution. The results showed that, using the SDS/PVP system, the critical coagulation concentration is about five times higher than that observed in the literature for suspension colloidaly stable at high concentration. The nano-suspension was also found to be very stable at ambient temperature and at different pH conditions. Desorption test confirmed the high affinity between API and wetting/dispersing agent. However, the suspension undergoes aggregation at high temperature due to the desorption of the wetting/dispersing agent and disaggregation of SDS micelles. Furthermore, aggregation occurs at very high shear rate (orhokinetic aggregation) by overcoming the energy barrier responsible for colloidal stability of the system.

Viscoelastic properties of sterically stabilised emulsions and their stability.

The interaction forces between emulsion droplets containing adsorbed polymeric surfactants and the theory of steric stabilisation are briefly described. The results for the viscoelastic properties of O/W emulsions that are stabilised with partially hydrolysed poly(vinyl acetate) that is commonly referred to as poly(vinyl alcohol) (PVA) with 4% vinyl acetate are given. The effect of the oil volume fraction, addition of electrolytes and increasing temperature is described. This allows one to obtain various parameters such as the adsorbed layer thickness, the critical flocculation concentration of electrolyte (CFC) and critical flocculation temperature (CFT) at constant electrolyte concentration. The viscoelastic properties of O/W emulsions stabilised with an A-B-A block copolymer of polyethylene oxide (A) and polypropylene oxide (B) are described. These emulsions behave as viscoelastic liquids showing a cross-over-point between G' (the elastic component of the complex modulus) and G″ (the viscous component of the complex modulus) at a characteristic frequency. Plots of G' and G″ versus oil volume fraction ϕ show the transition from predominantly viscous to predominantly elastic response at a critical volume fraction ϕ(c). The latter can be used to estimate the adsorbed layer thickness of the polymeric surfactants. Results are also shown for W/O emulsions stabilised with an A-B-A block copolymer of polyhydroxystearic acid (PHS, A) and polyethylene oxide (PEO, B). The viscosity volume fraction curves could be fitted to the Dougherty-Krieger equation for hard-spheres. The results could be applied to give an estimate of the adsorbed layer thickness Δ which shows a decrease with increase of the water volume fraction. This is due to the interpenetration and/or compression of the PHS layers on close approach of the water droplets on increasing the water volume fraction. The last section of the review gives an example of O/W emulsion stability using an AB(n) graft copolymer of polyfructose (A) to which several C12 alkyl chains are grafted. The emulsions are stable both at high temperature and in the presence of high electrolyte concentrations (2 mol dm(-3) NaCl). This high stability is due to the strong adsorption ("anchoring") of the graft copolymer with several C12 alkyl chains and the strong hydration of the polyfructose chains both in water and in the presence of high electrolyte concentrations and temperature. Evidence for this high stability is obtained using disjoining pressure measurements which show a highly stable film between the emulsion droplets and absence of its rupture up to high pressures.

Engineering of nano-crystalline drug suspensions: employing a physico-chemistry based stabilizer selection methodology or approach.

This paper describes a systematic approach to select optimum stabilizer for the preparation of nano-crystalline suspensions of an active pharmaceutical ingredient (API). The stabilizer can be either a dispersant or a combination of dispersant and wetting agent. The proposed screening method is a quick and efficient way to investigate a large number of stabilizers based on the principles of physical-chemistry and employs a stepwise approach. The methodology has been divided in two main parts; the first part being focused on the qualitative screening with the objective of selecting the best candidate(s) for further investigation, the second part has been focused on quantitative screening with the objective to optimize the ratio and amount of wetting and dispersing agents, based on wettability, surface charges measurement, adsorption evaluation, process-ability evaluation and storage stability. The results showed clearly that SDS/PVP 40/60% (w/w) (sodium dodecyl sulfate/poly(vinyl pyrrolidone)) at a total concentration of 1.2% was the optimum stabilizer composition, at which the resulting nanosuspensions were stable for more than 50 days at room temperature.

Rheological investigations on the creaming of depletion-flocculated emulsions.

Preventing creaming or sedimentation by the addition of thickeners is an important industrial challenge. We study the effect of the addition of a "free" nonadsorbing polymer (xanthan gum) on the stability against creaming of sterically stabilized O/W emulsions. Therefore, we analyze our samples using microscopy and rheological measurements. At low xanthan concentrations, the emulsions cream. However, above a certain concentration a three-dimensional network of droplets is formed, which can prevent creaming. We attribute the formation of this structure to depletion attraction. The rheological behavior of an emulsion that is macroscopically stable should be elastic, while it should be viscous for a creaming emulsion. In order to distinguish between stable and unstable samples, we measure their relaxation time by mechanical rheology and find a good correlation to the visual observation. However, the measured relaxation times are much shorter than the time-scales, on which we observe creaming. We hypothesize that the measured relaxation time is related to the droplet-droplet interaction. This determines the frequency at which microscopic rearrangements occur, which weaken the network structure prior to creaming. Based on this interpretation, the relaxation time gives direct access to the microstructural processes involved in creaming. We therefore suggest using it as a predictive parameter of creaming stability.

Interparticle interactions in concentrated suspensions and their bulk (rheological) properties.

The interparticle interactions in concentrated suspensions are described. Four main types of interactions can be distinguished: (i) "Hard-sphere" interactions whereby repulsive and attractive forces are screened. (ii) "Soft" or electrostatic interactions determined by double layer repulsion. (iii) Steric repulsion produced by interaction between adsorbed or grafted surfactant and polymer layers. (iv)and van der Waals attraction mainly due to London dispersion forces. Combination of these interaction energies results in three main energy-distance curves: (i) A DLVO type energy-distance curves produced by combination of double layer repulsion and van der Waals attraction. For a stable suspension the energy-distance curve shows a "barrier" (energy maximum) whose height must exceed 25kT (where k is the Boltzmann constant and T is the absolute temperature). (ii) An energy-distance curve characterized by a shallow attractive minimum at twice the adsorbed layer thickness 2δ and when the interparticle-distance h becomes smaller than 2δ the energy shows a sharp increase with further decrease of h and this is the origin of steric stabilization. (iii) an energy-distance curve characterized by a shallow attractive minimum, an energy maximum of the DLVO type and a sharp increase in energy with further decrease of h due to steric repulsion. This is referred to as electrosteric repulsion. The flocculation of electrostatically and sterically stabilized suspensions is briefly described. A section is devoted to charge neutralization by polyelectrolytes and bridging flocculation by polymers. A distinction could be made between "dilute", "concentrated" and "solid suspensions" in terms of the balance between the Brownian motion and interparticle interaction. The states of suspension on standing are described in terms of interaction forces and the effect of gravity. The bulk properties (rheology) of concentrated suspensions are described starting with the case of very dilute suspensions (the Einstein limit with volume fraction Φ≤0.01), moderately concentrated suspensions (0.2>Φ≥0.1) taking into account the hydrodynamic interaction and concentrated suspensions (Φ>0.2) where semi-empirical theories are available. The rheological behavior of the above four main types of interactions is described starting with "hard-sphere" systems where the relative viscosity-volume fraction relationship could be described. The rheology of electrostatically stabilized suspensions was described with particular reference to the effect of electrolyte that controls the double layer extension. The rheology of sterically stabilized systems is described using model polystyrene suspensions with grafter poly(ethylene oxide) layers. Finally the rheology of flocculated suspensions was described and a distinction could be made between weakly and strongly flocculated systems.

Interaction forces between adsorbed polymer layers.

The interaction forces between adsorbed polymer layers were investigated. Two types of graft copolymers that were adsorbed on hydrophobic surfaces have been investigated: (i) a graft copolymer consisting of polymethylmethacrylate/polymethacrylic acid back bone (the B chain) on which several poly(ethylene oxide) chains are grafted (to be referred to as PMMA/PEO(n)); and (ii) a graft copolymer consisting of inulin (linear polyfructose with degree of polymerization >23) (the A chain) on which several C(12) chains are grafted (INUTEC SP1). In the first case adsorbed layers of the graft copolymer were obtained on mica sheets and the interaction forces were measured using the surface force apparatus. In the second case the interaction forces were measured using Atomic Force Microscopy (AFM). For this purpose a hydrophobically modified glass sphere was attached to the tip of the cantilever of the AFM and the glass plate was also made hydrophobic. Both the sphere and the glass plate contained an adsorbed layer of INUTEC SP1. In the surface forces apparatus one essentially measures the energy E(D)-distance D curves for the graft copolymer of PMMA/PEO(n) between mica surfaces bearing the graft copolymer and this could be converted to interaction energy between flat surfaces. Using the de Gennes scaling theory, it is possible to calculate the interaction energy between the polymer layers. The same graft copolymer was used in latex dispersions and the high frequency modulus G'(∝) was measured as a function of the volume fraction Φ of the dispersion. This high frequency modulus could be related to the potential of mean force. In this way one could compare the results obtained from rheology and those obtained from direct measurement of interaction forces. In the AFM method, the interaction forces are measured in the contact area between two surfaces, i.e. a spherical glass particle and a glass plate. Both glass spheres and plates were hydrophobized using dichlorodimethylsilane. Results were obtained for adsorbed layers of INUTEC SP1 in water and in the presence of various concentrations of Na(2)SO(4) (0.3, 0.8, 1.0 and 1.5 mol dm(-3)). All results showed a rapid increase of force with a decrease of separation distance and the forces were still repulsive up to the highest Na(2)SO(4) concentration. This explains the high stability of dispersions when using INUTEC SP1 as stabilizer.

Use of hydrophobically modified inulin for the preparation of polymethyl methacrylate/polybutyl acrylate latex particles using a semicontinuous reactor.

The seeded semicontinuous emulsion copolymerization of methyl methacrylate (MMA) and butyl acrylate (BuA) stabilized with a graft polymeric surfactant based on inulin, INUTEC SP1, as well as its mixture with sodium lauryl sulfate (SLS) is described. The mixture of SLS and Brij58 (alcohol ethoxylated) and the mixture of SLS and Pluronic P85 (block copolymer PEO-PPO-PEO) are also used as surfactant systems. The addition of methacrylic acid (MAA) or acrylic acid (AA) as comonomers is also studied. Previous results proved this inulin-derivative surfactant, INUTEC SP1, to be very effective on synthesizing latexes using a very low surfactant concentration. The kinetic features of the emulsion polymerization (instantaneous conversion and total conversion) were gravimetrically determined along the reactions. Latex dispersions were characterized by photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) to obtain the average particle size, the particle size distributions (PSDs) as well as the polydispersity index (PdI). The stability was determined by turbidimetry measurements and expressed in terms of critical coagulation concentration. The results showed that the use of the graft polymeric surfactant allowed obtaining highly stable nanoparticles, at low surfactant concentrations and high solid contents (up to 37 wt %). This is an improvement with respect to previous works, in which a mixture of the graft polymeric surfactant with another surfactant was required to obtain stable nanoparticles with low polydispersity, at high solid content. In the present work, low polydispersity was achieved using INUTEC as the only emulsifier, which was related to the absence of secondary nucleations. When a mixture of INUTEC SP1 and SLS is used, a wider PSD is obtained due to secondary nucleations. Replacing INUTEC SP1 by other nonionic surfactants such as Brij58 or Pluronic P85 leads to an increase of average particle size and wider PSD.

Polymeric surfactants in disperse systems.

This overview starts with a section on general classification of polymeric surfactants. Both homopolymers, block and graft copolymers are described. The solution properties of polymeric surfactants is described by using the Flory-Huggins theory. Particular attention is given to the effect of solvency of the medium for the polymer chains. The adsorption and conformation of homopolymers, block and graft copolymers at the solid/liquid interface is described. The theories of polymer adsorption and their predictions are briefly described. This is followed by a description of the experimental techniques that can be applied to study polymeric surfactant adsorption. Examples of adsorption isotherms of non-ionic polymeric surfactants are given. The effect of solvency on the adsorption amount is also described. Results for the adsorbed layer thickness of polymeric surfactants are given with particular attention to the effect of molecular weight. The interaction between particles containing adsorbed layers is described in terms of the unfavorable mixing of the stabilizing chains when these are in good solvent conditions. The entropic, volume restriction or elastic interaction that occurs on considerable overlap is also described. Combination of these two effects forms the basis of the theory of steric stabilization. The energy-distance curve produced with these sterically stabilized systems is described with particular attention of the effect of the ratio of adsorbed layer thickness to droplet radius. Examples of oil-in-water (O/W) and water-in-oil (W/O) emulsions stabilized with polymeric surfactants are given. Of particular interest is the O/W emulsions stabilized using hydrophobically modified inulin (INUTEC((R))SP1). The emulsions produced are highly stable against coalescence both in water and high electrolyte concentrations. This is accounted for by the multipoint attachment of the polymeric surfactant to the oil droplets with several alkyl groups and the strongly hydrated loops and tails of linear polyfructose. Evidence of this high stability was obtained from disjoining pressure measurements. Stabilization of suspensions using INUTEC((R))SP1 was described with particular reference to latexes that were prepared using emulsion polymerization. The high stability of the latexes is attributed to the strong adsorption of the polymeric surfactant on the particle surfaces and the enhanced steric stabilization produced by the strongly hydrated polyfructose loops and tails. Evidence for such high stability was obtained using Atomic Force Microscopy (AFM) measurements. The last part of the overview described the preparation and stabilization of nano-emulsions using INUTEC((R))SP1. In particular the polymeric surfactant was very effective in reducing Ostwald ripening as a result of its strong adsorption and the Gibbs elasticity produced by the polymeric surfactant.

Viscoelastic properties of polystyrene and poly(methyl methacrylate) dispersions sterically stabilized by hydrophobically modified inulin (polyfructose) polymeric surfactant.

Recently, steric repulsive forces induced by a new graft copolymer surfactant, which is based in inulin (polyfructose), have been described. Previous investigations by atomic force microscopy between solid surfaces covered with adsorbed surfactant indicated strong repulsive forces even at high electrolyte concentration, due to the steric repulsion produced by the surfactant hydration. In the present paper, the colloidal stabilization provided by this surfactant is studied by rheology. The measurements were carried out on sterically stabilized polystyrene (PS) and poly(methyl methacrylate) (PMMA) containing adsorbed surfactant (INUTEC SP1). Steady-state shear stress as a function of shear rate curves was established at various latex volume fractions. The viscosity volume fraction curves were compared with those calculated using the Doughtry-Krieger equation for hard sphere dispersions. From the experimental eta r-phi curves the effective volume fraction of the latex dispersions could be calculated and this was used to determine the adsorbed layer thickness Delta. The value obtained was 9.6 nm, which is in good agreement with that obtained using atomic force microscopy (AFM). Viscoelastic measurements of the various latex dispersions were carried out as a function of applied stress (to obtain the linear viscoelastic region) and frequency. The results showed a change from predominantly viscous to predominantly elastic response at a critical volume fraction (phi c). The effective critical volume fraction, phi eff, was calculated using the adsorbed layer thickness (Delta) obtained from steady-state measurements. For PS latex dispersions phi eff was found to be equal to 0.24 whereas for PMMA phi eff=0.12. These results indicated a much softer interaction between the latex dispersions containing hydrated polyfructose loops and tails when compared with latices containing poly(ethylene oxide) (PEO) layers. The difference could be attributed to the stronger hydration of the polyfructose loops and tails when compared with PEO. This clearly shows the much stronger steric interaction between particles stabilized using hydrophobically modified inulin.

Interaction forces between particles stabilized by a hydrophobically modified inulin surfactant.

The adsorption isotherm of a hydrophobically modified inulin (INUTEC SP1) on polystyrene (PS) and poly(methyl methacrylate) (PMMA) particles was determined. The results show a high affinity isotherm for both particles as expected for a polymeric surfactant adsorption. The interactions forces between two layers of the hydrophobically modified inulin surfactant adsorbed onto a glass sphere and plate was determined using a modified atomic force microscope (AFM) apparatus. In the absence of any polymer, the interaction was attractive although the energy of interaction was lower than predicted by the van der Waals forces. The results between two layers of the adsorbed polymer confirms the adsorption isotherms results and provides an explanation to the high stability of the particles covered by INUTEC SP1 at high electrolyte concentration. Stability of dispersions against strong flocculation could be attributed to the conformation of the polymeric surfactant at the solid/liquid interface (multipoint attachment with several loops) which remains efficient at Na(2)SO(4) concentration reaching 1.5 mol dm(-3). The thickness of the adsorbed polymer layer in water determined both by AFM and rheology measurements, was found to be about 9 nm.

Interaction forces in thin liquid films stabilized by hydrophobically modified inulin polymeric surfactant. 1. Foam films.

Using the interferometric method of Scheludko-Exerowa for investigation of foam films, we have obtained results using a hydrophobically modified inulin polymeric surfactant (INUTEC SP1). Measurements were carried out at constant INUTEC SP1 concentration of 2 x 10(-)(5) mol.dm(-)(3) and at various NaCl concentrations (in the range 1 x 10(-)(4) to 2 mol.dm(-)(3)). At constant capillary pressure of 50 Pa, the film thickness decreased gradually with an increase in NaCl concentration up to 10(-)(2) mol.dm(-)(3) NaCl above which the film thickness remains virtually constant at about 16 nm. This reduction in film thickness with an increase in NaCl concentration is due to the compression of the double layer and at the critical electrolyte concentration (C(el,cr) = 10(-)(2) mol.dm(-)(3)) the electrostatic component of the disjoining pressure is completely screened and the remaining pressure is due to the steric interaction between the adsorbed polymer layers. Disjoining pressure-thickness (Pi-h) isotherms were obtained at C(el) < C(el,cr) (10(-)(4) - 10(-)(3) mol.dm(-)(3)) and C(el) > C(el,cr) (0.5, 1, and 2 mol.dm(-)(3)). In the first case, the disjoining pressure isotherms could be fitted using the classical DLVO theory, Pi = Pi(el) + Pi(vw), and using the constant charge model. At C(el) > C(el,cr), the main repulsion is due to the steric interaction between the polyfructose loops that exist at the air-water interface, i.e., Pi = Pi(st) + Pi(vw). Under these conditions, there is a sharp transition from DLVO to non-DLVO forces. In the latter case, the interaction could be described using the de Gennes' scaling theory. This gave an adsorbed layer thickness of 6.5 nm which is in reasonable agreement with the values obtained at the solid-solution interface. The Pi-h isotherms showed that these foam films are not very stable and they tend to collapse above a critical capillary pressure (of about 1 x 10(3) Pa), and these results could be used to predict the foam stability.

Principles of emulsion stabilization with special reference to polymeric surfactants.

This overview summarizes the basic principles of emulsion stabilization with particular reference to polymeric surfactants. The main breakdown processes in emulsions are briefly described. A section is devoted to the structure of polymeric surfactants and their conformation at the interface. Particular attention is given to two polymeric surfactants that are suitable for oil-in-water (O/W) and water-in-oil (W/O) emulsions. For O/W emulsions, a hydrophobically modified inulin (HMI), obtained by grafting several alkyl groups on the backbone of the inulin (polyfructose) chain, is the most suitable. For W/O emulsions, an A-B-A block copolymer of polydroxystearic acid (PHS), the A chains, and polyethylene oxide (PEO), the B chain, is the most suitable. The conformation of both polymeric surfactants at the O/W and W/O interfaces is described. A section is devoted to the interaction between emulsion droplets containing adsorbed polymer surfactant molecules. This interaction is referred to as steric stabilization, and it is a combination of two main effects, namely, unfavorable mixing of the A chains, referred to as the mixing interaction, Gmix, and loss of configurational entropy on significant overlap of the stabilizing chains, referred to as elastic interaction, Gel. The criteria for effective steric stabilization are summarized. O/W emulsions based on HMI are described, and their stability in water and in aqueous electrolyte solutions is investigated using optical microscopy. Very stable emulsions can be produced both at room temperature and at 50 degrees C. The reason for this high stability is described in terms of the multipoint anchoring of the polymeric surfactant (by several alkyl groups), the strong hydration of the inulin (polyfructose) chains, and the high concentration of inulin in the adsorbed layer. W/O emulsions using PHS-PEO-PHS block copolymer can be prepared at a high volume fraction of water, varphi, and these emulsions remain fluid up to high varphi values (> 0.6). These emulsions also remain stable for several months at room temperature and at 50 degrees C. The last two sections are concerned with the problems of creaming or sedimentation and phase inversion. Creaming or sedimentation can be prevented by the use of "thickeners" in the continuous phase. These molecules produce non-Newtonian systems that will have a high residual or zero shear viscosity. The latter, which may exceed 1000 Pas, can also be prevented by control of the bulk (or elastic) modulus of the system. Phase inversion in O/W emulsions can also be prevented using HMI, since this polymeric surfactant is not soluble in the oil phase. As long as coalescence and Ostwald ripening are prevented, the emulsions can remain stable for very long times both at room temperature and at 50 degrees C.

Emulsion polymerization of styrene and methyl methacrylate using a hydrophobically modified inulin and comparison with other surfactants.

The use of a new class of graft polymer surfactants, based on inulin, in emulsion polymerization of poly(methyl methacrylate) (PMMA) and polystyrene (PS) particles is described. PS and PMMA were synthesized by emulsion polymerization, and stable particles with a high monomer content (50 wt %) were obtained with a very small amount of polymeric surfactant ([surfactant]/[monomer] = 0.0033). The latex dispersions were characterized by dynamic light scattering and by transmission electron microscopy to obtain the average particle size and the polydispersity index, and the stability was determined by turbidimetry measurements and expressed in terms of critical coagulation concentration. The last section gives a comparison of PMMA particles prepared by emulsion polymerization using classical surfactants from different types as emulsifiers with that obtained using the copolymer surfactant. It shows the superiority of INUTEC SP1 as it is the only one that allows stable particles at 20 wt % monomer content, with a smaller ratio [surfactant]/[monomer] = 0.002.

Light-sensitive fusion between polymer-coated liposomes following physical anchoring of polymerisable polymers onto lipid bilayers by self-assembly.

Delivery of therapeutics (drugs, radionuclides or genes) in vivo can be optimized when carried by a targeting delivery vehicle such as a surfactant vesicle, polymeric micelle or other polymer-coated colloidal particulate. In the present communication, we propose a general method based on self-assembly principles, to construct lipid-polymer bilayer vesicles whose featured characteristics may be altered according to the polymer molecule used, thus be easily designed along the needs of a particular delivery application. Polymer molecules containing non-polymerizable (polypropylene) and polymerisable (methacrylate) hydrophobic groups were used to construct lipid-polymer vesicles by following two different methods of preparation. In accord with our previous findings, when both types of polymer molecules are added to pre-formed liposomes, only weak adsorption onto the lipid surface occurs. Preparation of the vesicles by pre-mixing the lipid and polymer molecules has proved essential in order to allow the hydrophobic blocks of the copolymers to participate as integral parts of the bilayer. Anchoring of a polymerisable polymer onto the lipid bilayer by hydrophobic interactions, resulted in steric stabilization of the vesicles. When UV polymerization of the bilayer-incorporated [Methyl(PEG)2000MA] polymer was induced, inter-vesicle fusion was triggered. Direct cryo-EM imaging of fusion between the PEG-coated liposomes has been observed. Such sterically stabilised fusogenic vesicles were constructed as potential triggered-release delivery systems, responsive to a variety of external stimuli depending on the type of polymerisable, hydrophobic group in the polymer molecule. By altering the properties of the incorporated hydrophobic group, liposomes able to fuse in response to initiators milder than UV light, such as green or red light, sound, temperature, oxygen or pH can be engineered.

Application of rheology for assessment and prediction of the long-term physical stability of emulsions.

This review deals with the use of rheology for assessment and prediction of the long-term physical stability of emulsions. It starts with an introduction, highlighting the importance of having accelerated test to predict emulsion stability. This is followed by a section on the stability/instability of emulsion systems, giving a brief summary of the driving force of each instability process and its prevention. The classical techniques that can be applied for assessment of creaming or sedimentation, flocculation, Ostwald ripening, coalescence and phase inversion are briefly described. This is followed by several sections on the application of rheological techniques to assess and predict each of these instabilities. This involves the use of steady state shear stress-shear rate measurements, constant stress (creep) measurements and dynamic (oscillatory) techniques. The last section gives an example of model emulsions to illustrate the correlation between the various break-down processes with the rheological characteristics of the system.

Formation and stability of nano-emulsions.

This review describes the principles of formation and stability of nano-emulsions. It starts with an introduction highlighting the main advantages of nano-emulsions over macroemulsions for personal care and cosmetic formulations. It also describes the main problems with lack of progress on nano-emulsions. The second section deals with the mechanism of emulsification and the dynamic light scattering technique for measurement of the droplet size of nano-emulsions. This is followed by a section on methods of emulsification and the role of surfactants. Three methods are described for nano-emulsion preparation, namely high energy emulsification (using homogenisers), low energy emulsification whereby water is added to an oil solution of the surfactant and the principle of the phase inversion temperature (PIT). A section is devoted to steric stabilisation and the role of the adsorbed layer thickness. The problem of Ostwald ripening (which is the main instability process of nano-emulsions) is described in some detail. The methods that can be applied to reduce Ostwald ripening are briefly described. This involves the addition of a second less soluble oil phase such as squalene and/or addition of a strongly adsorbed and water insoluble polymeric surfactant. The last part of the review gives some examples of nano-emulsions that are prepared by the PIT method as well as using high pressure homogeniser. A comparison of the two methods is given and the rate of Ostwald ripening is measured in both cases. The effect of changing the alkyl chain length and branching of the oil was investigated using decane, dodecane, tertadecane, hexadecane and isohexadecane. The branched oil isohexadcecane showed higher Ostwald ripening rate when compared with a linear chain oil with the same carbon number.

Interaction forces between particles containing grafted or adsorbed polymer layers.

The interaction forces between particles containing grafted or adsorbed polymer layers have been investigated using rheological and surface force measurements. Polystyrene latex dispersions with grafted poly(ethylene oxide) (PEO) chains (M=2000) were used for the rheological measurements. Results were also obtained for latex dispersions stabilised with adsorbed graft copolymers of poly(methyl methacrylate-methacrylic acid) with methoxy capped PEO chains (M=750). The relative viscosity eta(r)-volume fraction phi curves for the latex dispersions with grafted PEO chains were established for three particle radii of 77.5, 306 and 502 nm. For comparison the eta(r)-phi curve was calculated using the Dougherty-Krieger equation. This allows one to obtain the adsorbed layer thickness delta as a function of phi. The results showed a decrease of delta with increase of phi, which was attributed to the interpenetration and/or compression of the PEO chains on increasing phi. Viscoelastic measurements as a function of phi showed a change from predominantly viscous to predominantly elastic response at a critical volume fraction, which indicated the onset of the strong steric repulsion when the polymer layers begin to overlap. A similar trend was obtained with the latex particles containing adsorbed graft copolymer layers. A scaling law was used to fit the elastic part of the logG'-log phi curve (where G' is the elastic modulus). This fit could be used to estimate the compressibility of the PEO chains. The correlation of the rheology of concentrated sterically stabilised dispersions with interparticle interactions was investigated by measuring the energy-distance curves for the graft copolymer that was adsorbed on smooth mica sheets. Using de Gennes scaling theory, it was possible to calculate the energy of interaction between the polymer layers. The high frequency modulus of the latex dispersions was obtained as a function of the volume fraction and the results were compared with those calculated from the potential of the mean force. The trends in the variation of the modulus with volume fraction were similar for the experimental rheological results and those calculated using the directly measured interaction forces. The above results demonstrated the powerful use of rheological measurements for studying the interaction between sterically stabilised dispersions in concentrated systems.