Kenneth A. Walters

Dermatological and transdermal formulations

The structure and function of the skin common skin disorders and their topical treatment basic mathematical principles in skin permeation skin transport methods for studying percutaneous absorption formulation strategies for modulating skinpermeation formulation and development of dermatological dosage forms bioequivalence of dermal and transdermal formulations scale-up of dermatological dosage forms a case for multivariate optimization and product homogeneity transdermal drug deliverysystems safety considerations for dermal and transdermal products transdermal delivery and cutaneous reactions.

Dermal absorption and toxicity assessment

The relationship between structure and barrier function of skin dermal metabolism systemic toxicity in man secondary to percutaneous absorption. Part 1 Modelling of dermal risk assessment: occupational skin disease - a case study current issues inthe in vitro measurement of percutaneous absorption investigation of the skin permeation in vitro prediction -physiological models prediction - simple risk models and overview of dermal risk assessment cutaneous microdialysis for human in vivo dermalabsorption studies physicochemical determinants of stratum corneum permeation. Part 2 Pharmeceuticals: in vitro/in vivo correlations in transdermal drug delivery irritancy of topical chemicals and transdermal delivery systems chemical penetrationenhancement - possibilities and problems drugs used for skin diseases drugs for pain and inflammation site of effects iontophoresis topical therapeutic agents used in wound care. Part 3 Cosmetics: regulation of cosmetics in the United States experimental design considerations and use of in vitro skin penetration data in cosmetic risk assessment percutaneous absorption of hair dyes sunscreens - toxicological aspects exposure to fragrances - their absorption and potential toxicity. Part 4Environmental: dermal absorption and toxicity assessment human skin penetration by metal compounds soil contamination -theoretical descriptions percutaneous absorption of hazardous substances from soil and water bathing water - percutaneous absorptionof water contaminants ultrastructural effects of some solvents and vehicles on the stratum corneum and other skin components - evidence for an extended mosaic-partitioning model of the skin barrier.

Prediction of the percutaneous penetration of ultra‐violet filters used in sunscreen formulations

The application of a mathematical model to estimate the extent of transdermal absorption of UV‐filters commonly used in sunscreen formulations is described. Percutaneous penetration is not a factor that has been properly addressed in the literature and the penetration/time profiles generated here suggest that significant amounts of certain of these compounds may penetrate the skin and enter the systemic circulation. The results presented indicate that further research in this area is necessary and the authors suggest that in vitro experiments with human skin are conducted with both current and new UV filters to quantify the degree of dermal penetration of these substances.

Surfactant effects in percutaneous absorption I. Effects on the transdermal flux of methyl nicotinate

Abstract We have investigated the effects of a series of surfactants on the permeability of human skin in vitro using methyl nicotinate as a model drug. The surfactants used were cetyl trimethyl ammonium bromide, sodium lauryl sulphate, decyl methyl sulphoxide and Brij 36T. These surfactants have a linear alkyl chain of 10–12 units linked to different hydrophilic groups. We found that while the ionic surfactant exerted a greater effect on the flux of methyl nicotinate, the nonionic surfactants had a smaller but more immediate effect on the flux. This is consistent with the hypothesis that for compounds to disturb the permeability barrier of the stratum corneum they must first penetrate it themselves. Ionic compounds can be expected to penetrate this lipophilic barrier more slowly than nonionic compounds of a similar structure and therefore will take longer to elicit their effects.

Some factors affecting the in vitro penetration of ibuprofen through human skin

Abstract The influence of various factors on the permeation of ibuprofen across human skin in vitro was determined. Permeation was increased by increasing the volume fraction of water in binary water-transcutol solvent mixtures, probably due to changes in thermodynamic activity. Permeation was also increased in the presence of nonionic surfactants based on an oleyl alkyl chain although this effect was saturable. The data confirmed that it is possible to develop improved formulation strategies to optimise the delivery of ibuprofen across the skin.

Dermatalogic, cosmeceutic, and cosmetic development: Therapeutic and novel approaches

Recent advances in our understanding of the development and morphology of normal skin have led to improved methods to deliver therapeutic compounds to selected targeted areas both within the skin and systemically. This reference provides a clear overview of pharmaceutical and cosmetic practices, drugs, and therapies to manage and treat major and minor skin disorders. Written for scientists interested in dermatological therapy and marketers of pharmaceutical and cosmetic products, the text is also useful for students developing strong research methods. The book covers drugs used to manage a range of skin disorders and the site where the effect is sought. It examines the efficiency and delivery of topical therapies, including various pharmaceutical therapies. It also explains how percutaneous absorption is affected by age, skin, site, race, skin disease, and damage and product form. Particular emphasis is on novel treatment approaches for major skin diseases and injuries pertaining to wounds and burns.

Surfactant effects in percutaneous absorption II. Effects on protein and lipid structure of the stratum corneum

Abstract The effects of several known penetration enhancers on the lipid structure of human stratum corneum have been investigated by differential scanning calorimetry. Effects on the birefringence were also examined. A correlation was found to exist between the ability of a compound to increase the birefringence of the stratum corneum and its reported tendency to induce local irritation when applied to the skin.

Surfactant effects in topical drug availability

Abstract The effects of two surfactants, sodium lauryl sulphate (SLS) and Brij 36T on the thermodynamic activity of methyl nicotinate (MN) and hexyl nicotinate (HN) in aqueous gels have been investigated. In vivo, the permeability of the skin has been assessed by measuring the time of onset of the erythema which is induced by these nicotinate esters. Times of onset of erythema caused by gels containing SLS correlate with the in vitro release rates. This suggests that over this time interval (less than 15 min) SLS does not affect the barrier function of the skin. Results obtained for Brij 36T-containing gels, however, imply that this surfactant does increase skin permeability. That SLS is normally considered to be the more powerful penetration enhancer yet has no observable effect indicates that the two surfactants exert their effect in different ways.

Skin penetration enhancement

One of the major problems in delivering drugs via the dermal route is the very effective barrier function of the skin. The reason for the barrier function can be attributed to the intercellular lipids of the stratum corneum. They are arranged into bilayer arrays and a penetrating drug has to be soluble in them and then transfer sequentially from a polar to a non-polar environment. Chemical enhancers act in a number of ways and the relative effects are often difficult to determine. If an enhancer diffuses into the stratum corneum it can alter the solubility properties of the skin lipids and hence modify partitioning of the drug. Additionally, some enhancers appear to disrupt the ordered nature of the bilayers; the increased fluidity facilitates diffusion of the permeant through the alkyl chain regions of the bilayers. Synergistic effects can be seen when enhancers are present which both aid solubility of the drug and increase the lipid disordering. Another approach to increasing the drug flux is to increas...

Measurement of diffusional parameters in membranes using ATR‐FTIR spectroscopy

The use of ATR‐FTIR spectroscopy for the assessment of synthetic and biological membrane permeability is described. Measurement of the diffusion coefficient of acetonitrile in a polydimethylsiloxane membrane showed the method to be of reasonable reproducibility. It has been demonstrated that the concurrent measurement of both solvent and solute permeability is feasible and that the deconvolution of the diffusion and partition coefficients of these species is theoretically possible. Where the diffusing species changed the nature of the membrane a correcting normalization routine was performed by assessing the state of the membrane as a function of time. The use of this method for the routine investigation of membrane permeation phenomena has great potential for the future.