Jean-Louis Grossiord

Influence of lipophilic surfactant on the release kinetics of water-soluble molecules entrapped in a W/O/W multiple emulsion

Abstract The aim of this work was to study the release kinetics of a water-soluble drug from two different W/O/W multiple emulsions prepared with two lipophilic surfactants at different concentrations. The study of the kinetics under both iso-osmotic and hypo-osmotic conditions allowed us to distinguish between two possible release mechanisms: swelling-breakdown or facilitated diffusion. The results obtained indicate that water-soluble drug release occurs by a mechanism of swelling followed by a breakdown of the oil globules, in which the lipophilic surfactant is a decisive factor. It appears that the globules swelling capacity is considerably increased when the lipophilic surfactant concentration increases, and the more the oil globule swells, the less the water-soluble drug releases. It seems that the stability could be improved by increasing the lipophilic surfactant concentration which could strengthen the interfacial film. In contrast, an excess of hydrophilic surfactant destabilized the emulsion.

Transdermal delivery of glucose through hairless rat skin in vitro: effect of multiple and simple emulsions

Abstract Three types of oil–water emulsions (W/O/W, O/W and W/O emulsions) were obtained and evaluated on hairless rat skin biopsies, using Franz diffusion cells. Natural emulsifiers (soybean phospholipids) were used to formulate stable multiple and simple emulsions. The qualitative and quantitative composition of the three emulsions was the same. In order to compare the emulsions that have been prepared with this new utilization of soybean phospholipids as emulsifier for vesicular systems and to achieve the importance of application conditions on the diffusion of glucose, a finite dose in open-cap and an infinite dose with occlusion were evaluated. After 24 h of diffusion, the maximum flux (0.69±0.21 μ g/cm 2 /h) for a finite dose was obtained with simple O/W emulsion, with a rank order of emulsions identical when compared to an infinite dose application: O/W>W/O/W>W/O.

Kinetics of swelling-breakdown of a W/O/W multiple emulsion: possible mechanisms for the lipophilic surfactant effect.

The properties and behavior of a W/O/W multiple emulsion formulation were analyzed during a swelling-breakdown process. Various experimental analyses, such as granulometry, rheology and conductimetry were performed, as well as a micropipette aspiration method. The predominant role of the lipophilic surfactant during the swelling phase confirmed. Two different mechanism can be proposed. Both imply the migration of the lipophilic surfactant from one interface to another and probably take place successively. The lipophilic surfactant could diffuse from the first to the second interface, thus rigidifying the membrane, or from the oily phase to the first interface, resulting in delayed coalescence of the aqueous droplets during swelling.

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

PURPOSEnThe 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.nnnMETHODSnOnce 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.nnnRESULTSnThe 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.nnnCONCLUSIONnAdditionally, 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.

Rheology: how to characterize and to predict the evolution of W/O/W multiple emulsions

The purpose of this work was to compare the evolution of three multiple emulsions (ME) by different controls. The series of water‐in‐oil‐in‐water (W/O/W) multiple emulsions were elaborated and controlled by both the usual analyses which permitted the classification of the multiple emulsions with respect to their thermal stability, and the rheological oscillatory and flow analyses which are polyvalent methods. Further, these allow the ‘identity card’ of the multiple emulsion to be drawn, its evolution to be followed, and moreover, its behaviour being foreseen by simulating ageing by shear. Three different behaviours are observed; a destructuration, a phase inversion and stability.

Vehicle influence on in vitro release of glucose: w/o, w/o/w and o/w systems compared

Abstract The in vitro release and percutaneous absorption of glucose as a hydrophilic model drug from oil/water (o/w), water/oil/ water (w/o/w) and water/oil (w/o) emulsions has been studied. All the emulsions were prepared with exactly the same composition in order to avoid any influence of the formulation. The glucose release studied with a cellulose membrane was nonlinear and fastest in case of the o w emulsion. In contrast, the release from w o emulsion was linear and the slowest. Release from w/o/w emulsion was non-linear and intermediate in rate. The release with a silicone membrane was linear from three emulsions studied and presented the same rank order. The rate of release for o/w, w/o/w and w/o emulsions was found to be 0.10, 0.036 and 0.014 μg/cm2/h respectively. The in vitro percutaneous absorption data of glucose indicate the same rank order as that observed with synthetic membranes. However, when compared with the release across the silicone membrane the differences between the emulsions increased considerably and only the w o emulsion reached a steady-state rate of absorption during the 30 h test period. The w/o/w emulsion showed some tendency toward steady state during the first 3–12 h and the flex was found to be 1.7 times greater than that from w/o emulsion. The total uptake of glucose in whole skin was found to be in following order: o w > w/o/w > w/o; this in good agreement with the results of the studies of absorption. Differences between o/w and w/o/w emulsions could be attributed to differences in the effective glucose concentration of their external aqueous phase. Differences between w/o/w and w/o emulsions could be attributed to the stratum corneum/vehicle partition coefficient.

Evaluation of two fluorescent probes for the characterization of W/O/W emulsions

Abstract The aims of this work were to select the most convenient fluorescent probe for the characterization of the W/O/W emulsion and to propose a new technique in order to study the release mechanism from the W/O/W emulsion. For this purpose fluorescence was compared with the well established conductimetric measurements using MgS0 4 .7H 2 0 as electrolyte. Two fluorescent molecules were evaluated: 5,(6)-carboxyfluorescein (5,(6)-CF) and 1,3,6,8, pyrene tetrasulfonic acid, tetrasodium salt (PTSA). After their introduction in the inner aqueous phase of the W/O/W emulsions; their stability (in aqueous solutions) to temperature and to light, their sensitivity at different pH conditions and to the presence of the constituents of the inner aqueous phase, their partition between the different phases of the emulsions and their influence on theological properties of the emulsions were analysed. PTSA was finaly selected as the most convenient probe due to its high stability at different conditions and its excellent yield of encapsulation. After the release studies, a satisfying correlation between HPLC fluorescence and conductimetry was obtained. Both techniques confirm that the release mechanism of the multiple emulsion is swelling-breakdown.

Paraquat detoxication with multiple emulsions

In this study, we show that detoxifying W/O/W multiple emulsions, prepared with an appropriate extractant/trapping couple, represent a promising technology for quick and safe poisoning treatments, with application to the highly toxic herbicide Paraquat, responsible of poisonings from low-dose exposure leading to several deaths every year. In vitro tests led to the choice of an appropriate extractant/trapping couple system with significant detoxication performance. In vivo tests showed (i) that rats receiving high doses of Paraquat, then a detoxifying emulsion, presented an increase from 50% to 100% of the MST (median survival time) and (ii) that no mortality was observed during 30 days with rats dosed with emulsions initially loaded with Paraquat at a concentration much higher than the lethal dose, proving the stability and the inocuity of the detoxifying multiple emulsion in the gastrointestinal tract.

Mixed O/W emulsions stabilized by solid particles: A model system for controlled mass transfer triggered by surfactant addition

This article deals with a model mixed oil-in-water (O/W) emulsion system developed to study the effect of surfactants on mass transfer between dispersed oil droplets of different composition. In this purpose, our goal was to formulate O/W emulsions without any surface active agents as stabilizer, which was achieved by replacing surfactants by a mixture of hydrophilic/hydrophobic silica particles. Then, to study the specific role of surfactants in the oil transfer process, different types and concentrations of surfactants were added to the mixed emulsion after its preparation. In such a way, the same original emulsion can be used for all experiments and the influence of various surface active molecules on the oil transfer mechanism can be directly studied. The model mixed emulsion used consists of a mixture of hexadecane-in-water and tetradecane-in-water emulsions. The transfer between tetradecane and hexadecane droplets was monitored by using differential scanning calorimetry, which allows the detection of freezing and melting signals characteristic of the composition of the dispersed oil droplets. The results obtained showed that it is possible to trigger the transfer of tetradecane towards hexadecane droplets by adding surfactants at concentrations above their critical micellar concentration, measured in presence of solid particles, through micellar transport mechanism.