Gilberte Marti-Mestres

Emulsions in Health Care Applications—An Overview

ABSTRACT Pharmaceutical applications of emulsions are reviewed with special emphasis on the main reasons these vehicles are used and on their limitations. The development of current applications and future directions are considered according to their delivery routes: these routes can be either parenteral, ocular, or oral, or even transdermal. We examine the raw materials generally used in the formulation of these emulsions, and we consider the main factors influencing the release and absorption of the drugs from these vehicles. We also treat the pharmaceutical applications of emulsified vehicles, particularly submicron emulsions, multiple emulsions, and microemulsions. We have also developed some interesting applications of these formulations such as self-emulsifying drug delivery systems, fat emulsions, and drug carrier systems.

LC analysis of benzophenone-3: II application to determination of ‘in vitro’ and ‘in vivo’ skin penetration from solvents, coarse and submicron emulsions

The aim of this study was to determine the skin penetration of benzophenone-3 in vitro and in vivo in order to investigate a possible influence of formulation. Six different vehicles, three solvents and three different emulsion types were evaluated in vitro and in vivo. Each vehicle was applied to the skin model at 2 mg cm(-2). First, histological studies on ear pigskin and human skin were evaluated. In vitro measurements were performed with static diffusion cells using pigskin at 1, 2, 4, and 8-h. In vivo, benzophenone-3 concentration in stratum corneum was evaluated by the stripping method after 30-min application on forearm of volunteers. It was shown that ear pigskin and human skin appear similar and in both experiments significant differences between vehicles were noticed. The six vehicles could be ranked in the same order of benzophenone-3 skin concentration. At 8-h, the highest concentration of benzophenone-3 in skin was obtained with propylene glycol, and O/W submicron emulsion. On the contrary. the two oily solvents. W/O emulsion and O/W coarse emulsion restrain the concentration of this UV-filter in the skin. At each time, permeability in vitro and in vivo were well correlated. Low concentrations were measured in the receptor fluid suggesting that percutaneous absorption of this UV-filter across the skin would be minimal. The in vitro and in vivo skin penetration capacity of benzophenone-3 from six vehicles was confirmed and quantified. A satisfactory relationship between binary in vitro and in vivo was established.

Benzophenone-3: rapid prediction and evaluation using non-invasive methods of in vivo human penetration

The study described in this paper constitutes a practical assay system to evaluate in vivo drug penetration using two complementary non-invasive methods. An electrical capacitance test was first applied to the skin on the forearm to evaluate the hydration of the skin, and check the integrity of the stratum corneum. In the first step, the percentage absorption was measured using an occlusive and difference method; following benzophenone-3 application any residual formulation was washed off and the amount removed analyzed. In the second step, the tape stripping method-a useful procedure for selectively removing the skins outermost layer, the stratum corneum, and measuring the stratum corneum adsorption-was performed. Under these conditions the human skin permeation of this UV-filter over four hours was near to 35% of the applied dose with the occlusive method. The amount of topically applied benzophenone-3 found in the stratum corneum after 30 min exposure using the stripping procedure was evaluated at 4% to the applied dose.

The influence of alcohol, propylene glycol and 1,2-pentanediol on the permeability of hydrophilic model drug through excised pig skin

Alcohol and glycol including 1,2-pentanediol, a new product in this field, were examined for their transdermal penetration enhancing in vitro properties using pig skin and caffeine as a model drug. In order to investigate a possible influence of these compounds, we followed diffusion from an aqueous solution with caffeine followed by a series of different vehicles, their compositions were: (1) in water as a control; (2) in propylene glycol/ethanol/water (25:25:48; v/v/v); (3) in 1,2-pentanediol/water (2.5:95.5, v/v); (4) in 1,2-pentanediol/water (5:93, v/v); in propylene glycol/water (5:93; v/v); and in ethanol/water (5:93; v/v). The stratum corneum/vehicle partition coefficients (K(m)), maximum flux (J), enhancement factor (EF), 24-h receptor concentration (Q(24h)) were determined and compared to control values (caffeine in water). Permeation was also expressed in percentage of the applied dose absorbed in the different compartments. In all test models, caffeine was released and penetrated into pig skin. The 1,2-pentanediol was presented as the most effective enhancer; with a low proportion of this compound (only 5%), caffeine penetrated the skin quicker and in a greater extent. While this compound showed promise as penetration enhancer, further study was required to determine its effectiveness with others drugs and its irritation potential.

Emulsion Formulations: Study of the Influence of Parameters with Experimental Designs

AbstractParameters of formulation of emulsions were performed by the aid of experimental designs. The aim of the work was to investigate five factors at two levels: temperature of manufacture, time of phase introduction, rate of homogenization, mode of cooling, and operators. The study of the flow behavior of the emulsions corresponds to the quantitive response. This work allowed us to show the dominating influence of the factor “mode of cooling”. The progressive cooling at room temperature gives a better stability than the brutal cooling with a water bath corresponding to a shorter homogenization. A further aim was to study the influence of an additional factor: the nature of the sulfactant with the best mode of cooling, progressive cooling. In that case, we can conclude that the main factor, the nature of the surfactant, influences the response.

Irradiation of skin and contrasting effects on absorption of hydrophilic and lipophilic compounds.

Increasing legal requirements for risk assessment and efficacy testing in the dermo‐cosmetic field have led to the development of alternative test methods. In this study, the porcine skin model was chosen to test the effect of irradiation on the penetration habits of UV filters and caffeine. For decades, the pig has been recognized as an experimental animal in biomedical research thanks to its morphological and physiological similarities to humans. In this study, we wanted to investigate the effect of UV irradiation on the absorption of octocrylene (OC) and benzophenone‐3 (B3) sunscreens used under those circumstances and a model hydrophilic molecule, caffeine (Caf). These particular compounds were chosen due to their different lipophilic profiles. The percutaneous penetration of the two UV filters and Caf was studied after two simulated solar radiation doses of 61.4 kJ m−2. After irradiation simulation, the total absorbed dose was increased for OC while for B3 and Caf it was lower. Thus, modifications in percutaneous absorption have been observed, and it appears that UV could play a crucial role in this process. Moreover, it has been observed that the lipophilic profile of the studied compounds affects percutaneous penetration when irradiated.

Stability of UV Filters in Different Vehicles: Solvents and Emulsions

AbstractIn this paper, we analyzed the stability of several ultraviolet (UV) filters exposed to simulated solar light. Evaluation of the photostability of UV-A/UV-B filters has an important impact on the efficiency of sunscreen preparations. The purpose of this study is first to relate some of the solvent shifts that can interact with UV filters; secondly, it is to formulate sunscreen emulsions (oil in water and water in oil) in order to evaluate the photostability of sunscreens in the mixture, and therefore their efficiency in solar protection, because photostability and protection are closely linked together.

Optimization with Experimental Design of Nonionic, Anionic, and Amphoteric Surfactants in a Mixed System

AbstractIn a mixture experiment the response depends only on the relative proportions of material present in the mixture. In this study, we consider shampoo formulations with three different classes of surface-active agents: amphoteric, nonionic, and anionic mild sufactants. A major purpose of this study is to help the formulator with a strategy using a three-component simplex-centroid design. This methodology offers the maximum return in terms of information about the interplay of multiple factors while requiring the minimum investment.

Skin Constituents as Cosmetic Ingredients. Part II: A Study of Bio‐Mimetic Monoglycerides Behavior at the Squalene‐Water Interface by the “Pendant Drop” Method in a Dynamic Mode

This work aims at presenting the viscoelastic behavior of bio‐mimetic monoglycerides used as emulsifier in a mixture made of two non‐miscible liquids, squalene and water. The measurement of the interfacial tension, carried out by the “pendant drop” method in “dynamic” mode, made it possible to characterize these amphiphilic molecules according to the value of their elastic modulus, ϵ, as well as their relaxation time, τR. The analysis of these parameters, as well as those developed in the previous publication [L. Blasco et al. (2006) Skin constituents as cosmetic ingredients. Part I: A Study of bio‐mimetic monoglyceride behavior at the squalene‐water interface by the “pendant drop” method in a static mode. J. Dispers. Sci. Technol., 27(6).] shows that the hydrocarbon chain structure, such as its length, the presence of one or more unsaturations, hydroxyl function, affects the behavior of surfactant molecules at the squalene/water interface.

Modification of the droplet size and distribution of parenteral emulsions by tangential microfiltration

In this work we studied the modification of the droplet size and distribution of stable parenteral emulsions (PEs) by microfiltration. The intravenous nutrition through PE needs to be conducted using very fine emulsified fat droplets, which have to be for health reasons at a mean diameter under 1 μm. In this work we used membrane microfiltration to decrease the fat particles mean diameter and distribution. The PE filtration was possible without coalescence, because of the high stability of the PE prepared by using an emulsification method never applied before to this type of emulsion. The membrane filtration process was carried out by using ceramic membranes with different pore sizes (0.8, 1.2 and 1.4 μm of mean pore radius). The results obtained showed that the shearing forces and trans-membrane pressure had a fundamental influence on the emulsion droplet size distribution and that depending on the membrane type or operating conditions used, the mean droplet size and distribution could be effectively decreased.