Permeability coefficients and vapour pressure determination for fragrance materials.

OBJECTIVE: This study aims to correlate new experimental data relevant to the description of the combined evaporation/permeation process of a perfume applied onto the skin. METHODS: The vapour pressure data were measured by thermogravimetric analysis (TG-DTA). The Antoine constants and the Clarke and Glew parameters were determined for the same set of fragrance molecules to describe its low vapour pressures at new temperature ranges. The permeability coefficient of a set of 14 fragrance molecules in ethanolic solution was determined by Franz diffusion cell experiments, using porcine skin. The samples were analysed by gas chromatography with a flame ionization detector (GC/FID) and high-performance liquid chromatography with UV visible detector (HPLC/UV). A QSAR model was proposed to correlate the experimental data. RESULTS: The Antoine constants were determined and presented low standard deviations. The Clarke and Glew physically significant parameters were obtained along with its statistical analysis. The fitting is good since the magnitude order is in accordance with the literature, associated with the low correlation between the estimated parameters and low standard deviations. The presented correlation, based on a mixture using only ethanol as solvent, showed better results than previous QSAR models with a standard relative deviation ( σ r ) of 0.190, a standard error (SE) of 0.397 and a determination coefficient (R2 ) of 0.7786. CONCLUSION: The dataset is still small compared to larger and more general QSAR models; however, it is much more specific as to the type of solvent and class of materials studied. This work represents an advance for the modelling of the perfume diffusion process since it specifies important properties that until then had been treated in a more general way.

OBJECTIF: Cette étude vise à corréler de nouvelles données expérimentales pertinentes à la description du processus combiné d'évaporation/perméation d'un parfum appliqué sur la peau. MÉTHODES: Les données de pression de vapeur ont été mesurées par analyse thermogravimétrique (TG-DTA). Les constantes d'Antoine et les paramètres de Clarke & Glew ont été déterminés pour le même ensemble de molécules de parfum afin de décrire ses faibles pressions de vapeur à de nouvelles plages de température. Le coefficient de perméabilité d'un ensemble de 14 molécules de parfum en solution éthanolique a été déterminé par des expériences de cellules de diffusion de Franz, en utilisant de la peau de porc. Les échantillons ont été analysés par chromatographie en phase gazeuse avec un détecteur à ionisation de flamme (GC / FID) et chromatographie liquide haute performance avec détecteur UV visible (HPLC / UV). Un modèle QSAR a été proposé pour corréler les données expérimentales. RÉSULTATS: Les constantes d'Antoine ont été déterminées et ont présenté de faibles écarts types. Les paramètres physiquement significatifs de Clarke & Glew ont été obtenus avec son analyse statistique. L'ajustement est bon car l'ordre de grandeur est conforme à la littérature, associé à la faible corrélation entre les paramètres estimés et les faibles écarts types. La corrélation présentée, basée sur un mélange utilisant uniquement de l'éthanol comme solvant, a montré de meilleurs résultats que les modèles QSAR précédents avec un écart relatif standard (σr) de 0,190, une erreur standard (SE) de 0,397 et un coefficient de détermination (R2) de 0,7786. CONCLUSION: L'ensemble de données est encore petit par rapport aux modèles QSAR plus grands et plus généraux ; cependant, il est beaucoup plus spécifique quant au type de solvant et à la classe de matériaux étudiés. Ce travail représente une avancée pour la modélisation du processus de diffusion des parfums car il précise des propriétés importantes jusque-là traitées de manière plus générale.

A New Approach to Ex Vivo Permeation Studies in In-Situ Film-Forming Systems.

The skin is the largest human organ and an important topical route. Even with some challenges, it is an important ally in medication administration, mainly because it is painless and easy-to-apply. Semisolid formulations are the most used dosage forms for drug administration via this delivery route and can be optimized when transformed into a film, favoring on-site maintenance, and promoting drug permeation. However, in situ film-forming systems are difficult to assess and characterize using Franz-type diffusion cells once this apparatus is ideal to formulations without transition phases. The present study proposed a different method to characterize these formulations and provide complementary data on drug and penetration enhancer behaviors, as close as possible to real application conditions. This characterization method allowed us to analyze drug concentration on three necessary occasions: remaining in the polymer film, stratum corneum using adhesive tape, and skin to check where drugs will have a desirable effect. As a proof-of-concept, the proposed ex vivo permeation method was used to evaluate a film-forming system containing lidocaine and prilocaine. We could also evaluate transition phases of drug compositions and quantify drugs at key times after application. Hence, the developed method may be used to provide complementary data to the Franz diffusion cell method, in terms of drug and penetration enhancer behaviors incorporated into film-forming delivery systems.

Development of a Discriminative In Vitro Release Test for Rivastigmine Transdermal Patches Using Pharmacopeial Apparatuses: USP 5 and USP 6.

The aim of this study was to develop and validate a discriminating in vitro release test to evaluate rivastigmine transdermal patches. The Exelon® Patch was chosen as a model transdermal product. The studies of in vitro release were designed to determine the impact of the official apparatus chosen (USP apparatus 5 and USP apparatus 6), the rotation speed, and the dissolution medium characteristics on the rivastigmine release profile from transdermal patches. Patches with different drug release profiles were tested in order to evaluate the discriminating power of the in vitro release test developed and validated. Variables such as the apparatus type, the dissolution medium, and the rotation speed have a significant influence on the drug release characteristics from a transdermal patch. The in vitro release methodologies using the USP apparatus 5 at 50 rpm and USP apparatus 6 at 25 rpm using the medium phosphate-buffered saline pH 7.4 were considered discriminative and adequate to characterize the rivastigmine (RV) release from a commercial transdermal patch, Exelon® Patch.

Comparative evaluation of rivastigmine permeation from a transdermal system in the Franz cell using synthetic membranes and pig ear skin with in vivo-in vitro correlation.

In the present study, in vitro permeation experiments in a Franz diffusion cell were performed using different synthetic polymeric membranes and pig ear skin to evaluate a rivastigmine (RV) transdermal drug delivery system. In vitro-in vivo correlations (IVIVC) were examined to determine the best model membrane. In vitro permeation studies across different synthetic membranes and skin were performed for the Exelon(®) Patch (which contains RV), and the results were compared. Deconvolution of bioavailability data using the Wagner-Nelson method enabled the fraction of RV absorbed to be determined and a point-to-point IVIVC to be established. The synthetic membrane, Strat-M™, showed a RV permeation profile similar to that obtained with pig ear skin (R(2)=0.920). Studies with Strat-M™ resulted in a good and linear IVIVC (R(2)=0.991) when compared with other synthetic membranes that showed R(2) values less than 0.90. The R(2) for pig ear skin was 0.982. Strat-M™ membrane was the only synthetic membrane that adequately simulated skin barrier performance and therefore it can be considered to be a suitable alternative to human or animal skin in evaluating transdermal drug transport, potentially reducing the number of studies requiring human or animal samples.

Effect of pectins on the mass transfer kinetics of monosaccharides, amino acids, and a corn oil-in-water emulsion in a Franz diffusion cell.

The effect of high (HMP) and low (LMP) methoxylated pectins (2%w/w) on the rate and extent of the mass transfer of monosaccharides, amino acids, and a corn oil-in-water emulsion across a cellulose membrane was evaluated. A sigmoidal response kinetic analysis was used to calculate both the diffusion coefficients (rate) and the amount of nutrients transferred through the membrane (extent). In all cases, except for lysine, HMP was more effective than LMP in inhibiting both the rate and extent of the mass transfer of nutrients through the membrane. LMP and HMP, e.g., reduced 1.3 and 3.0times, respectively, the mass transfer rate of glucose, as compared to control (containing no pectin), and 1.3 and 1.5times, respectively, the amount of glucose transferred through the membrane. Viscosity, molecular interactions, and flocculation were the most important parameters controlling the mass transfer of electrically neutral nutrients, electrically charged nutrients, and emulsified lipids, respectively.

Development of ciclopirox olamine topical formulations: evaluation of drug release, penetration and cutaneous retention.

With the aim of reducing system absorption and consequently, the side effects, and simultaneously select a penetration enhancing, three topical formulations with 0.5% ciclopirox olamine (CO) and 15% of propylene glycol (PG), ethoxydiglycol or oleic acid were developed and evaluated regarding the skin penetration and cutaneous retention of the drug using Franz diffusion cells. Release experiments were performed through synthetic membrane while dermatomed pig ear skin was used to evaluate CO skin penetration and skin retention. Retention studies were carried out applying tape stripping method and dosing CO in stratum corneum and in epidermis and dermis. A HPLC method was validated for quantifying CO. All formulations tested with synthetic membrane presented no retention of the drug. Permeation data suggested that there was no systemic absorption of ciclopirox olamine from the studied formulations, even when the skin penetration enhancers were applied. Higher concentrations of the drug were found in the stratum corneum (SC) and also in epidermis and dermis, for all of the developed formulations. The addition of enhancers improved the penetration and cutaneous retention of CO, and propylene glycol promoted higher concentrations in epidermis and dermis, probably because its cumulative effect on the skin and by an efficient solvent power.