Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport.

Memantine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of moderate to severe dementia including the symptoms of Alzheimer's disease (AD). It is administered orally but compliance, swallowing problems and the routine use of multiple medications in elderly AD patients means that an alternative route of administration would be of interest. The aim of the present study was to develop memantine hydrochloride occlusive transdermal therapeutic systems (TTS) for passive and iontophoretic delivery across the skin. Polyvinyl pyrrolidone (PVP) and a mixture with polyvinyl alcohol (PVA) were employed as polymeric matrices. The study involved the TTS characterization in addition to quantification of the memantine transport across porcine skin in vitro. The evaluation of the TTS physical properties suggested that systems were made more mechanically resistant by including PVA (6%) or high concentrations of PVP (24%). Moreover, a linear correlation was observed between the concentration of PVP and the bioadhesion of the systems. Drug delivery experiments showed that the highest transdermal flux provided by a passive TTS (PVP 24% w/w limonene) was 8.89±0.81µgcm-2h-1 whereas the highest iontophoretic transport was 46.4±3.6µgcm-2h-1. These innovative TTS would enable two dosage regimens that could lead to therapeutic plasma concentrations.

Development of antimigraine transdermal delivery systems of pizotifen malate.

The aim of this study was to develop and evaluate a transdermal delivery system of pizotifen malate. Pizotifen is frequently used in the preventive treatment of migraine, but is also indicated in eating disorders. In the course of the project, the effects of chemical enhancers such as ethanol, 1,8-cineole, limonene, azone and different fatty acids (decanoic, decenoic, dodecanoic, linoleic and oleic acids) were determined, first using a pizotifen solution. Steady state flux, diffusion and partition parameters were estimated by fitting the Scheuplein equation to the data obtained. Among the chemical enhancers studied, decenoic acid showed the highest enhancement activity, which seemed to be due to the length of its alkyl chain and unsaturation at the 9th carbon. The influence of iontophoresis and the involvement of electrotransport in said process was determined. The absorption profile obtained with iontophoresis was similar to that obtained with fatty acids and terpenes, though skin deposition of the drug was lower with the former. Transdermal delivery systems (TDS) of pizotifen were manufactured by including chemical enhancers, decenoic acid or oleic acid, and were subsequently characterized. When the results obtained with solutions were compared with those obtained with the TDS, a positive enhancement effect was observed with the latter with respect to the partitioning and diffusion of the drug across the skin. Our findings endorse the suitability of our TDS for delivering therapeutic amounts of pizotifen malate.

Transdermal absorption of memantin--effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity.

The transdermal administration of memantine may have advantages with respect to oral therapy when treating advanced stages of Alzheimer's disease. With the ultimate objective of administrating memantine through a transdermal patch, the absorption of the drug across skin was evaluated by means of in vitro permeation studies. The effect of several chemical enhancers was studied in order to enhance percutaneous absorption of the memantine. The iontophoretic transdermal transport of memantine hydrochloride using a current density of 0.5 mA/cm(2) was also investigated. Results demonstrated that pre-treatment of the skin with R-(+)-limonene, laurocapram, decenoic acid, or oleic acid produced a statistically significant increment in the transdermal flux of memantine hydrochloride with respect to the control. Iontophoresis exhibited the greatest ability to enhance the flux of drug with respect to the control; nevertheless, the results obtained with R-(+)-limonene indicate that this compound could be of great use as a percutaneous enhancer in a memantine transdermal delivery system. In this study, the relationship between enhancement activity and lipophilicity was also studied. Satisfactory correlations have been obtained between the optimum lipophilicity of the enhancer and n-octanol/water partition coefficients of drugs. This relationship is a very useful tool that could allow to reduce time and to optimize the selection of appropriate enhancers for transdermal formulations.

Análisis de los factores de riesgo del cáncer de mama desde la farmacia comunitaria / Evaluation of risk factors of breast cancer in comunitary pharmacies

Introducción: El cáncer de mama es la neoplasia maligna más frecuente entre las mujeres, y en España es la que produce mayor número de muertes al año. La detección precoz propicia tratamientos menos agresivos y mayores tasas de curación. El objetivo de este estudio es analizar los factores de riesgo de las mujeres que acudieron a las ofi inas de farmacia participantes en el estudio: antecedentes familiares, edad y sexo, edad de concepción, enfermedad mamaria benigna, sobrepeso u obesidad, terapia hormonal (anticonceptivos orales o terapia hormonal sustitutiva), tabaco y alcohol. Material y métodos: En el estudio participaron cinco oficinas de farmacia de distintas provincias. Para el análisis de los factores de riesgo se entregó a las mujeres una breve encuesta que debían completar. Resultados y conclusiones: Tras analizar los factores de riesgo, se concluye que un 12% de las mujeres participantes tiene un riesgo elevado de padecer cáncer de mama. Desde la farmacia se puede informar a las mujeres sobre los factores de riesgo del cáncer de mama, con el fin de que apliquen las medidas necesarias para prevenir y/o detectar a tiempo esta enfermedad(AU)

Introduction: Cancer of breast is the malignant neoplasia more frequent between the women; in Spain it is the one that produces major number of deaths in a year. Early detection enables less aggressive treatments and the cure rate is greater. Objectives: In this study we analyze the following factors of risk: familiar precedents, age and sex, age of conception, mammary benign disease, overweight or obesity, hormonal therapy (oral contraceptives or hormonal substitute therapy), tobacco and alcohol of the women that came to the pharmacies. Material and methods: In the study there took part five pharmacies of different provinces. For the analysis of the factors of risk the woman was completing a brief questionnaire. Results and conclusions: The results indicate that 12% of the women participants have high risk of suffering cancer of breast. The pharmacist can form women on the risk factors of breast cancer to implement the necessary measures to prevent and/or detect early this disease(AU)

HPLC-UV analytical method for determination of pizotifen after in vitro transdermal diffusion studies.

Pizotifen malate is an antihistamine and serotonin inhibitor used in the preventive treatment of migraine and eating disorders. A simple, rapid, accurate and precise high-performance liquid chromatography (HPLC) method involving ultraviolet detection was validated for the quantitative analysis of pizotifen malate in samples from in vitro transdermal diffusion studies. The method was validated for specificity, linearity, accuracy, precision, limit of detection, limit of quantification and robustness. Drug stability in the solution was also determined under different conditions. Separation was carried out using a 250 × 4.0 mm Kromasil(®) C(18) column at room temperature. The detector response, fitted at 254 nm, was found to be linear in a concentration range between 0.24 and 24.0 µg/mL. The limit of detection was 0.02 µg/mL and the limit of quantification was 0.07 µg/mL. Finally, in vitro transdermal diffusion of pizotifen malate was characterized using the validated HPLC method.

Educación sanitaria en la farmacia comunitaria: estudio controlado en la provincia de Castellón / No disponible

Introducción: La educación para la salud es una de las actividades que debe realizar el farmacéutico comunitario orientada hacia el paciente. Con el objetivo de conocer la influencia de la educación sanitaria en los pacientes, se realizó un estudio controlado en farmacias comunitarias de la provincia de Castellón.Material y métodos: En el estudio participaron catorce oficinas de farmacia (siete en el grupo control y siete en el grupo intervención). En todas ellas se realizó una encuesta inicial a los pacientes sobre educación para la salud. En las farmacias del grupo intervención se realizaron cinco campañas de educación sanitaria y al finalizar cada campaña los pacientes completaron una encuesta para valorar la educación sanitaria recibida. En las farmacias del grupo control se pasaron las encuestas a los pacientes pero no se realizaron las campañas de educación sanitaria.Resultados y discusión: Los pacientes están significativamente más satisfechos con la formación que reciben en las farmacias que realizan educación sanitaria. Además, se incrementa significativamente la percepción que tiene la población del farmacéutico en la oficina de farmacia como punto de referencia a la hora de ayudar a resolver sus problemas de salud. La educación sanitaria permite que los pacientes reciban formación completa acerca de temas de salud que les preocupan y les proporciona más capacidad para resolverlos por ellos mismos(AU)

Introduction: Health education is one of the roles of the community pharmacist.A controlled study of pharmacies in the Spanish province of Castellón was carried out with the aim of determining the influence of health education on the general public.Material and methods: Fourteen pharmacies took part in the study: seven in the group control and seven in the intervention group. An initial survey about health education was conducted among the patients of all fourteen pharmacies. In the pharmacies in the intervention group five campaigns of health education were instigated; after each campaign patients answered a survey to evaluate the health education received. In the pharmacies in the control group the same surveys were carried out without the implementation of any educational campaigns.Results and discussion: Patients of the pharmacies in the intervention group were significantly more satisfied with their level of knowledge about health matters than those in the control other group. In addition, the same patients had a significantly more satisfied with the formation they received in the pharmacies that implemented the educational campaigns. In addition, patients of the pharmacies in the intervention group had a significantly better perception of the pharmacist and of the pharmacy as a reference point with respect to resolving their health problems. Health education informs patients about aspects of health and endows them with the aptitude to make decisions related to their health problems(AU)

Effect of iontophoresis on in vitro transdermal absorption of almotriptan.

The aim of the present work was to characterize the in vitro transdermal absorption of almotriptan through pig ear skin. The passive diffusion of almotriptan malate and its iontophoretic transport were investigated using current densities of 0.25 and 0.50mA/cm(2). In vitro iontophoresis experiments were conducted on diffusion cells with an agar bridge without background electrolytes in the donor compartment. Although both current densities applied produced a statistically significant increment with respect to passive permeation of almotriptan (p<0.01), that of 0.50mA/cm(2) proved to be the best experimental condition for increasing the transport of almotriptan across the skin. Under these experimental conditions, the transdermal flux of the drug increased 411-fold with respect to passive diffusion, reaching 264±24µg/cm(2)h (mean±SD). Based on these results, and taking into account the pharmacokinetics of almotriptan, therapeutic drug plasma levels for the management of migraine could be achieved via transdermal iontophoresis using a reasonably sized (around 7.2cm(2)) patch.

Implementación de un aula de la Farmacia en la Facultad de Ciencias de la Salud de la Universidad CEU - Cardenal Herrera / Implementation of Classroom of Pharmacy at the Faculty of Health Sciences

El Espacio Europeo de Educación Superior (EEES) supone un cambio en nuestras metodologíasdocentes, que deben orientarse hacia una mayor participación del alumno en el proceso de enseñanzaaprendizaje,así como a satisfacer la necesidad de formación del mundo laboral. Por ello, y en base a lanecesidad de nuestra Universidad de adaptar la docencia de Farmacia al Espacio Europeo deEducación Superior, la Facultad de Ciencias de la Salud de la Universidad CEU Cardenal Herrera, hadesarrollado un proyecto para implantar un aula que simule una Oficina de Farmacia.Entre los perfiles laborales del farmacéutico, el de Oficina de Farmacia es el más frecuente, por seresta la ocupación laboral mayoritaria. La labor en las farmacias comunitarias consiste básicamente enla conservación, dispensación, asesoramiento y elaboración de medicamentos. Todo ello, unido alejercicio de la atención farmacéutica, conlleva una gran carga de responsabilidad, un conocimiento yvigilancia de la legislación establecida al respecto y una base científica y técnica importante. Lafarmacia es, a su vez, un centro de educación y prevención sanitaria, dietética y cosmética.Con el objetivo de que nuestros alumnos desarrollen todas las competencias necesarias para elfarmacéutico en la Facultad de Salud se implantó el Aula de la Farmacia(AU)

The European Higher Education Area (EHEA) represents a shift in our teaching methodology, whichshould now be steered towards a greater participation of students in the teaching-learning process andshould satisfy the employment market’s need for trained professionals. In this context, our universityhas sought to adapt its pharmacy teaching programme to the EHEA, and so the Faculty of HealthSciences of the CEU Cardenal Herrera University has developed a project to create a space thatsimulates a working pharmacy.Among the different professional profiles within the discipline of pharmacy, a position in achemist’s/drugstore is the most common, as the majority of pharmacists are employed as such. Thework of community pharmacies basically consists of the storing, dispensing and preparation ofmedication. These tasks, combined with the pharmaceutical care provided to patients and customers,involve a great deal of responsibility that depends on knowledge and safeguarding of the currentlegislation and a solid scientific and technical training. A pharmacy is, at the same time, a centre ofeducation and prevention in health, diet and cosmetics(AU)

Transdermal iontophoresis of dexamethasone sodium phosphate in vitro and in vivo: effect of experimental parameters and skin type on drug stability and transport kinetics.

The aim of this study was to investigate the cathodal iontophoresis of dexamethasone sodium phosphate (DEX-P) in vitro and in vivo and to determine the feasibility of delivering therapeutic amounts of the drug for the treatment of chemotherapy-induced emesis. Stability studies, performed to investigate the susceptibility of the phosphate ester linkage to hydrolysis, confirmed that conversion of DEX-P to dexamethasone (DEX) upon exposure to samples of human, porcine and rat dermis for 7 h was limited (82.2+/-0.4%, 72.5+/-4.8% and 78.6+/-6.0% remained intact) and did not point to any major inter-species differences. Iontophoretic transport of DEX-P across dermatomed porcine skin (0.75 mm thickness) was studied in vitro as a function of concentration (10, 20, 40 mM) and current density (0.1, 0.3, 0.5 mA cm(-2)) using flow-through diffusion cells. Increasing concentration of DEX-P from 10 to 40 mM resulted in a approximately 4-fold increase in cumulative permeation (35.65+/-23.20 and 137.90+/-53.90 microg cm(-2), respectively). Good linearity was also observed between DEX-P flux and the applied current density (i(d); 0.1, 0.3, 0.5 mA cm(-2); J(DEX) (microg cm(2) h(-1))=237.98 i(d)-21.32, r(2)=0.96). Moreover, separation of the DEX-P formulation from the cathode compartment by means of a salt bridge - hence removing competition from Cl(-) ions generated at the cathode - produced a 2-fold increase in steady-state iontophoretic flux (40 mM, 0.3 mA cm(-2); 20.98+/-7.96 and 41.82+/-11.98 microg cm(-2) h(-1), respectively). Pharmacokinetic parameters were determined in Wistar rats (40 mM DEX-P; 0.5 mA cm(-2) for 5h with Ag/AgCl electrodes and salt bridges). Results showed that DEX-P was almost completely converted to DEX in the bloodstream, and significant DEX levels were achieved rapidly. The flux across rat skin in vivo (1.66+/-0.20 microg cm(-2) min(-1)), calculated from the input rate, was not statistically different from the flux obtained in vitro across dermatomed porcine skin (1.79+/-0.49 microg cm(-2) min(-1)). The results suggest that DEX-P delivery rates would be sufficient for the management of chemotherapy-induced emesis.

Development and evaluation of occlusive systems employing polyvinyl alcohol for transdermal delivery of sumatriptan succinate.

The aim of the present study was to develop a sumatriptan succinate transdermal system for applying migraine treatments efficiently and easily. For this system polyvinyl alcohol was employed as a matrix and Azone((R)) was added as a permeability enhancer. The physical characteristics, mechanical properties, and in vivo bioadhesion of the systems were evaluated, as was in vitro permeation across porcine skin. A uniform distribution of the drug in the matrix was observed, and moisture uptake values were constant. With regard to mechanical parameters, occlusive layer inclusion made the system more resistant, and no significant differences were detected with respect to other systems. Although Azone((R)) reduced the bioadhesivity of the systems, adherence to skin was maintained 24 h after application. Permeation studies showed that the systems formulated with Azone((R)) provided the highest permeability profiles for sumatriptan succinate.

Sumatriptan succinate transdermal delivery systems for the treatment of migraine.

We have successfully obtained sumatriptan transdermal systems with different polymer compositions: methyl cellulose (MC), polyvinyl pyrrolidone (PVP) and a polyvinyl pyrrolidone (PVP)-polyvinyl alcohol (PVA) mixture. The systems contained 1,2-propylenglycol (MC) or sorbitol as a plasticizer (PVP and PVP-PVA), methacrylate copolymer as an adhesive agent, and an occlusive liner. Azone (5%, w/w) was incorporated into all the systems as a percutaneous enhancer. Transdermal systems are thin, transparent and non-adhesive when in a dry state. The permeation of sumatriptan succinate across pig ear skin was studied using the systems prepared. The formulation with MC polymer produced a statistically significant increment with respect to the PVP and PVP-PVA formulations (p < 0.05). Azone incorporation into the systems produced an increment in the sumatriptan flux values of all three transdermal systems with respect to those of the controls (p < 0.05). In addition, the application of iontophoresis to the wet methyl cellulose-Azone formulation produced a much higher increase of sumatriptan transdermal flux.

Combination strategies for enhancing transdermal absorption of sumatriptan through skin.

The aim of the present work was to characterize in vitro sumatriptan transdermal absorption through human skin and to investigate the effect of chemical enhancers and iontophoresis applied both individually and in combination. A secondary objective was to compare the results obtained with those in porcine skin under the same conditions, in order to characterize the relationship between the two skin models and validate the porcine model for further research use. Transdermal flux of sumatriptan was determined in different situations: (a) after pre-treatment of human skin with ethanol, Azone (1-dodecyl-azacycloheptan-2-one), polyethylene glycol 600 and R-(+)-limonene, (b) under iontophoresis application (0.25 and 0.50 mA/cm(2)) and (c) combining chemical pre-treatment and iontophoresis at 0.50 mA/cm(2) current density. All the strategies applied enhance sumatriptan transdermal absorption. A linear relationship between the fluxes in the two skin models in the different conditions assayed can be established. The combination of both strategies, Azone and iontophoresis, proved to be the most effective of the techniques for enhancing the transdermal absorption of sumatriptan. The flux obtained with porcine skin in vitro is approximately double that obtained in human skin.

Bioadhesive monolayer film for the in vitro transdermal delivery of sumatriptan.

The work presented here aims to develop a bioadhesive monolayer film containing sumatriptan as adjuvant for the treatment of headache pain in a severe migraine attack. Permeation experiments were performed from the films prepared and from the respective solution, to evaluate the relevant permeation parameters. The effect of the penetration enhancers Transcutol, 2-pyrrolidone, and polyethylene glycol 600 was evaluated. The results obtained show that Transcutol and 2-pyrrolidone decreased sumatriptan permeation from solution, whereas a modest increase was produced by polyethylene glycol 600. The enhancers produced the same effects when they were included in the film. Compared to solution, the film showed a higher sumatriptan flux in the early times of the experiment. When the film was applied in occlusive conditions the profiles were much higher, indicating the importance of patch drying. Concerning skin retention, the bioadhesive film produced a reduction of the amount of sumatriptan remaining in the skin, but this can be advantageous in the control of drug input, since it reduces the reservoir effect in the skin and allows for an immediate interruption of drug input when the patch is removed.

Iontophoretic transdermal delivery of sumatriptan: effect of current density and ionic strength.

Iontophoretic transdermal delivery of sumatriptan was investigated in vitro. Among the conditions tested, 0.25 mA/cm2 and low ionic strength (NaCl 25 mM) was the best experimental condition to increase its transport across the skin. The flux increased 385-fold respective to passive diffusion, thus resulting in a transdermal flux of sumatriptan of 1273+/-83 nmol/cm2 h.

Effect of chemical enhancers on the in vitro percutaneous absorption of sumatriptan succinate.

The effects of percutaneous enhancers on the transdermal absorption of sumatriptan succinate were investigated by in vitro permeation studies. Pretreatment of porcine skin with ethanol (vehicle), polyethylene glycol 600, Span 20, oleic acid, R-(+)-limonene, alpha-bisabolol and 1,8-cineole (at 5% in ethanol, w/w) produced in all cases an increase in the flux of sumatriptan. The amount of sumatriptan retained in the skin was also determined. Ethanol has showed a low but significant increment on the drug transdermal flux. Treatment of the skin with alpha-bisabolol shows the same enhancer effect than ethanol. Span 20, oleic acid, and polyethylene glycol 600 have shown a moderate enhancing activity on transdermal flux of sumatriptan. R-(+)-limonene showed the greatest ability to enhance the flux of sumatriptan.

High-performance liquid chromatographic determination of sumatriptan after in vitro transdermal diffusion studies.

A simple, accurate, precise and rapid HPLC method with UV detection has been validated in order to determine the in vitro transdermal absorption of sumatriptan succinate. The HPLC method is a modification of that described by Nozal et al. [M.J. Nozal, J.L. Bernal, L. Toribio, M.T. Martin, F.J. Diez, J. Pharm. Biomed. Anal. 30 (2002) 285-291]. Separation was carried out on a 250 mm Kromasil C18 column at room temperature. The detector response, at 282.7 nm, was found to be linear in a concentration range between 0.145 and 145 microM. The limit of detection (LOD) was 0.019 microM and the limit of quantification (LOQ) was 0.145 microM.

Características y aplicaciones de la goma guar / Dispensation of drugs in the primary attention centers

La goma guar es un mucílago neutro que se obtiene por molturación del endospermo de las semillas de la planta Cyamopsis tetragonolobus (L.) Taub., que pertenece a la familia de las leguminosas. La goma guar es un polisacárido de galactomanana cuyo peso molecular oscila entre 220.000 ± 10% Daltons. Por cada unidad de galactosa hay entre 1.8 y 2 manosas. Se utiliza en numerosas aplicaciones tanto en la industria alimentaria como en otras industrias, como la textil, farmacéutica, del papel, refinado de aceites, explosivos e industria química. Su uso en alimentación es cada vez más frecuente, tiene un papel muy importante en las fases de presentación y de procesado de los alimentos. Se utiliza en sopas, postres, aliñados de ensaladas, comida congelada, bebidas, quesos suaves, yogures, mezclas instantáneas, productos de bollería, conservas y comida de niños, donde actúa como agente emulsificador, y estabilizador de las suspensiones, espesante y para mejorar la palatabilidad. Además tiene importantes aplicaciones terapéuticas en el tratamiento de la diabetes, obesidad, hipercolesterolemia, gastritis, úlceras gastroduodenales y estreñimiento

Guar gum is a neutral mucilage obtained of the ground endosperm of seeds of Cyamopsis tetragonolobus (L.) Taub. (Leguminosae). Guar gum is a galactomannane polysaccharide with a molecular weight between 220.000 ± 10% Daltons. There are between 1.8 - 2 mannose residues for every galactose residue. It is used in numerous food and non-food applications, such as textile, pharmaceutical, paper, oil well drilling, explosive and chemical industry. This gum has become increasingly common in food, as it plays an important role in processing stages and final presentation of the product. It is used in soups, desserts, salad dressings, deep frozen food, beverages, soft cheese, yoghurt, instant mixes, bakery products, confectionery, canned foods and baby foods, where it acts as emulsifier, stabiliser suspending agent, thickener and mouth feel improver. In addition it has important therapeutic applications in the treatment of DMNID, obesity, hypercholesterolemia, gastritis, gastroduodenal ulcer and constipation

The influence of Span20 on stratum corneum lipids in langmuir monolayers: comparison with Azone.

Recently we have proved that Span 20 has the same enhancer effect as Azone on in vitro percutaneous penetration of lipophilic compounds (logP(oct) from 1.34 to 2.33). The purpose of this work is to study the interactions of Span 20 with stratum corneum lipids monolayers and to compare them with Azone. The surface pressure-area characteristics of Span 20 in mixed monolayers with different model lipids (ceramides, cholesterol, free fatty acids and two mixtures of ceramides+cholesterol, and ceramides+cholesterol+free fatty acids) in similar proportions to that which exists in human stratum corneum lipids were recorded as compression isotherms at 25 degrees C. Azone was also investigated on monomolecular films of some of these lipids. The results indicate that the effect exerted upon lipid packing by the Span 20 correspond, as in the case of Azone, to increased fluidity within monolayers. To quantify and compare the effect of Span 20 and Azone, the compressibility of enhancer-lipid model mixed monolayers was calculated, and expressed as a function of mole fraction of enhancer present on the films. Statistical comparison of the results obtained from both enhancers shows that they are equally potent in their interaction with the lipid models assayed. These models, if restricted, seem to be good for predict the activity and potency of percutaneous enhancers on the fluididity of the lipidic structure of the stratum corneum.

An in vitro percutaneous absorption study of non-ionic compounds across human skin.

Generally, the mechanisms of percutaneous absorption are studied from correlations between representative penetration parameters (permeability coefficients) and variables accounting for lipophilicity or other related physicochemical properties. The present study was developed on the basis of the in vitro permeability coefficients through human skin, 280 microns in thickness, of a non-ionic homologous series of compounds (phenylalkanols). The corresponding penetration/lipophilicity correlations were compared with those found for a basic homologous series (4-n-alkylanilines) through a membrane of similar characteristics. The in vitro behaviour of both series of compounds may be regarded as similar. Differences were only observed in the permeability coefficients of those elements which in both series exhibited lipophilicity values above that considered optimum, as predicted by the selected biophysical penetration model. Consequently, it appears that the removal of the thick dermal tissue leads to increased permeation rates for the more lipophilic compounds and suggests that the dermis acts as an aqueous matrix.