Christian Surber

The tape stripping procedure ― evaluation of some critical parameters

Tape stripping is a simple and efficient method for the assessment of quality and efficacy of cosmetical and dermatological formulations. After topical application and penetration of formulations, the cell layers of the stratum corneum are successively removed from the same skin area using adhesive films. The tape strips contain the amount of corneocytes and the corresponding amount of the penetrated formulation, which can be determined by classical analytical chemical methods. Different formulations can strongly influence the amount of stratum corneum removed with every tape strip. Therefore, it is essential for the comparison of the penetration of different formulations that the amount of formulation detected on the single tape strip is not related to the tape strip number as a relative measure of the penetration depths, but to their standardized real position in the stratum corneum. Therefore, different methods are reported for the determination of the amount of stratum corneum removed with every tape strip. The tape stripping method in its standardized form is well-suited to determine the dermatopharmacokinetics of topically applied substances. Additionally, the method can be used to obtain information about the homogeneity and the distribution of formulations on the skin and in the stratum corneum. This is used, e.g., for the determination of the homogeneity of the distribution and the ex vivo determination of a universal sun protection factor (USPF) characterizing the efficacy of sunscreens.

Optimization of Topical Therapy: Partitioning of Drugs into Stratum Corneum

To optimize a topical formulation for therapeutic effect generally implies that the flux of drug into the skin be maximized. This requirement means that the product of drug concentration in the vehicle (Cv) and drug partition coefficient (PC) between stratum corneum (SC) and vehicle be as large as possible. While Cv is a formulation variable which can be easily manipulated up to the drugs saturation solubility, PC is a parameter that is difficult to predict a priori. However, there is no question that an ability to evaluate PC would greatly facilitate the efficient screening of drugs and formulations. We have measured the SC/water and SC/isopropylmyristate (a model lipophilic vehicle) PCs of seven drugs: acitretin, progesterone, testosterone, diazepam, estradiol, hydrocortisone, and caffeine. SC/ water PCs were determined as a function of the following variables: (i) initial drug concentration in the vehicle, (ii) length of equilibrium, (iii) SC source and preparation technique, and (iv) SC delipidization. The data obtained were reproducible and physicochemically consistent, and they show that useful partitioning information from both aqueous and nonaqueous vehicles can be obtained with the biological tissue of greatest relevance. The SC/water PCs of the steroids were in reasonable agreement with previous measurements. A facile approach to an integral determinant of formulation optimization is suggested, therefore, by these observations.

Effect of Concentration and Degree of Saturation of Topical Fluocinonide Formulations on In Vitro Membrane Transport and In Vivo Availability on Human Skin

AbstractPurpose. The thermodynamic acitvity of drugs in topical vehicles is considered to significantly influence topical delivery. In vitro diffusion across a synthetic membrane was shown to be correlated to the degree of saturation of the drug in the applied vehicle and therefore offers a potential for increased topical drug delivery. Fluocinonide a topical corticosteroid, was chosen as a model compound to investigate in vitro and in vivo availability from formulations with different degrees of saturation. Methods. Sub-, as well as, supersaturated drug solutions were prepared using PVP as an antinucleant agent. In vitro membrane diffusion experiments across silicone membrane and in vivo pharmacodynamic activity assessments, using the human skin blanching assay, were carried out. Results. Over the concentration range studied, the in vitro membrane transport of fluocinonide was proportional to the degree of saturation of the respective formulations. The in vivo pharmacodynamic response in the human skin blanching assay was related to the concentration of the drug in the vehicle irrespective of the degree of saturation. Conclusions. From the membrane permeation experiment it can be concluded, that the drug flux might be increased supra-proportionally with increasing donor concentration, drug (super-)saturation (proportional), beyond what would be anticipated based on ideal donor concentration and partition coefficient considerations only. These findings could not be confirmed in the in vivo investigation, probably due to additional vehicle effects (e.g., enhancement, irritation, drug binding) which have to be expected and could have altered the integrity of the stratum corneum and therewith topical bioavailability of the drug.

pDelayed‐type hypersensitivity to subcutaneous lidocaine with tolerance to articaine: confirmation by in vivo and in vitro tests

A 43‐year‐old woman suffered from recurrent localized swellings and an eczematous dermatitis starting 1 day after an injection of lidocaine. Intradermal patch and lymphocyte transformation tests revealed sensitization to lidocaine and cross‐reactivity to the other aminoacylamide local anesthetics bupivacaine. mepivacaine and prilocaine, but not to articaine. Contact allergy to the ester local anesthetics benzocaine, procaine and tetracaine, the quinoline or aminoalkylamide cinchocaine, and the preservatives methylparaben and metabisulfite, was excluded. A subcutaneous challenge with articaine was well tolerated.

Outdoor workers’ sun‐related knowledge, attitudes and protective behaviours: a systematic review of cross‐sectional and interventional studies

Sun protection is a major concern for outdoor workers as they are particularly exposed to solar ultraviolet radiation and therefore at increased risk of developing some forms of skin cancer, cataract and ocular neoplasm. In order to provide an overview of outdoor workers’ sun‐related knowledge, attitudes and protective behaviours as reported in the literature and to evaluate the effectiveness of sun‐safety education programmes in outdoor occupational settings, we conducted a systematic review of the literature by searching three electronic databases (PubMed, Embase, PsycINFO) from their inception up to 25 April 2012. An extensive hand search complemented the database searches. We identified 34 relevant articles on descriptive studies and 18 articles on interventional studies. Considerable numbers of outdoor workers were found to have sun‐sensitive skin types; sunburn rates per season ranged from 50% to 80%. Data concerning outdoor workers’ sun‐related knowledge and attitudes were scarce and controversial. The reported sun‐protective behaviours were largely inadequate, with many workers stating that they never or only rarely wore a long‐sleeved shirt (50–80%), sun‐protective headgear (30–80%) and sunscreen (30–100%) while working in the sun. However, there is growing evidence that occupational sun‐safety education is effective in increasing outdoor workers’ sun‐protection habits and presumably in decreasing sunburn rates. Occupational sun‐safety education programmes offer great potential for improving outdoor workers’ largely insufficient sun‐protective behaviours. It is hoped that, in the future, committed support from healthcare authorities, cancer foundations, employers and dermatologists will open the way for rapid and uncomplicated implementation of sun‐safety education programmes.

Nasal drug delivery in humans.

Intranasal administration is an attractive option for local and systemic delivery of many therapeutic agents. The nasal mucosa is--compared to other mucosae--easily accessible. Intranasal drug administration is noninvasive, essentially painless and particularly suited for children. Application can be performed easily by patients or by physicians in emergency settings. Intranasal drug delivery offers a rapid onset of therapeutic effects (local or systemic). Nasal application circumvents gastrointestinal degradation and hepatic first-pass metabolism of the drug. The drug, the vehicle and the application device form an undividable triad. Its selection is therefore essential for the successful development of effective nasal products. This paper discusses the feasibility and potential of intranasal administration. A series of questions regarding (a) the intended use (therapeutic considerations), (b) the drug, (c) the vehicle and (d) the application device (pharmaceutical considerations) are addressed with a view to their impact on the development of products for nasal application. Current and future trends and perspectives are discussed.

Tape-stripping technique

Tape stripping is a technique that has been found useful in dermatopharmacological research for selectively and, at times, exhaustively removing the skin’s outermost layer, the stratum corneum. Typically an adhesive tape is pressed onto the test site of the skin and is subsequently abruptly removed. The application and removal procedure may be repeated 10 to more than 100 times (1,2). Skin that has been stripped in this manner has been used as standardized injury in wound healing research. The technique has been adapted for studying epidermal growth kinetics (3–7), and it may also be useful as a diagnostic tool in occupational dermatology to assess the quality of the stratum corneum (8,9). The observation that the skin may serve as a reservoir for chemicals was originally reported by Malkinson and Ferguson in 1955 (10). The localization of this reservoir within the stratum corneum was later demonstrated for corticosteroids by Vickers in 1963 (11) and has been confirmed by others (12– 15). The introduction of the tape stripping method to further investigate the reservoir and barrier function of the skin gave a significant expansion to experimental tools in skin research (16–18). Differences in the permeability of intact and fully stripped skin have provided information about the diffusional resistance of the various dermal strata (19). It has been recognized that complete removal of the stratum corneum was not possible even after 30–40 strippings (20), and a certain barrier function in the tissue so treated remains (21,22). Öhman et al. showed that after 100 tape

Absorption of Topical Tacrolimus (FK506) in vitro through Human Skin: Comparison with Cyclosporin A

Cyclosporin A (CsA) is efficacious in many dermatoses as an oral but not as a topical form, while tacrolimus (FK506) has been shown to be effective in both forms. As inadequate skin absorption has been proposed as the reason for inefficacy of topical CsA, factors contributing to percutaneous absorption of FK506 and CsA were studied. Partitioning of FK506 and CsA between octanol and water, stratum corneum and water, and stratum corneum and isopropyl myristate was determined. Absorption of FK506 and CsA through dermatomed human cadaver skin was determined with in vitro flow-through cells. In partitioning experiments, CsA was more lipophilic than FK506. Both drugs were seen in comparable amounts in skin layers, but FK506 permeated the skin to a greater extent than CsA.

The Mystical Effects of Dermatological Vehicles

Topical treatment of the skin is as old as the evolution of man. Instinctively, we try to treat a skin injury or irritation with cooling or soothing substances. Even animals lick their wounds, trusting instinctively in the healing power of saliva. When did this archaic pattern of treatment take the gigantic leap from folk medicine to modern drug therapy? This text illustrates the evolution of topical dermatological vehicles, their application (guidelines) and future use. In particular, a phenomenon that has so far been ignored in product development and clinical testing is the vehicle metamorphosis. In clinical and experimental situations, most dermatological vehicles undergo considerable changes after they have been removed from the primary container and are applied to the skin. Subsequently, the initial structural matrix, and the quantitative composition of the vehicle, will most likely change during and after the mechanical shear associated with application of the product and/or evaporation of ingredients. This natural, but highly dynamic process will generate mini-environments for the active moiety that are difficult to predict and that are crucial to the fate of the active moiety. Despite the reasonable wishes of formulators, clinicians, patients and customers, there are still no universal vehicles. Each drug, at each concentration, requires a different vehicle for optimized therapy. Stability and compatibility of excipients and active moiety are crucial for any commercially available pharmaceutical or cosmetic formulation, together with local and systemic safety of all components. Nonetheless, more diverse and molecularly complex classes of new dermatological vehicles are continuously being researched and refined. The scientific progress has been remarkable when one considers the simple emulsion mixtures that were commonplace in dermatological therapy and still persist to this day in commercial products. It is to be hoped that the result of these research endeavors will be the emergence of more innovative topical formulations, applying engineered bioavailability control systems, with broader applications in topical therapeutic and cosmetic vehicles.

Topical retinoids in the management of photodamaged skin: from theory to evidence-based practical approach

Skin, being exposed directly to the environment, represents a unique model for demonstrating the synergistic effects of intrinsic and extrinsic factors on the ageing process. Ultraviolet radiation (UVR) is the major factor among exogenous stressors responsible for premature skin ageing. The problem of skin ageing has captured public attention and has an important social impact. Different therapeutic approaches have been developed to treat cutaneous ageing and to diminish or prevent the negative effects of UVR. Topical retinoids represent an important and powerful class of molecules in the dermatologist’s hands for the treatment of photodamaged skin. Since their introduction more than 20 years ago, topical retinoids have shown beneficial efficacy and good safety profiles in the management of photodamaged skin, and as therapeutic anti‐ageing agents. This review provides a brief retrospective of the development of topical retinoids in the treatment of photodamaged skin, elucidates their mechanism of action, delineates their use and addresses clinical, pharmaceutical and regulatory issues in connection with their intended use.