Evaluation of skin absorption of drugs from topical and transdermal formulations

Abstract

The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed. Uniterms:Skin absorption/effects/study. Skin absorption/topical formulations. Skin absorption/ transdermal formulations. Skin absorptions/enhancers. INTRODUCTIONTopical and transdermal drug delivery systems have shown significant advantages in clinical practice for drug targeting to the action site in the body; this has reduced the systemic side effects. The administration of drugs by through the skin is also performed to achieve controlled or prolonged drug delivery, and this route can be explored as an alternative to the oral route. The oral route shows some limitations for drugs with irregular absorption in the gastrointestinal tract and low bioavailability and for drugs with increased first pass metabolism and short plasma halflife times (Barry, 2001;Wokovich et al., 2006;Prausnitz, Langer, 2009;Alexander et al., 2012).Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected. This is the case for topical formulations for treatment of skin disorders such as acne and cutaneous inflammatory diseases that include dermatitis, erythematous lupus, and psoriasis. On the other hand, transdermal formulations release drugs that permeate through the skin and enter the systemic circulation. Transdermal therapy must ensure that significant concentrations of the drug are absorbed to reach effective plasma concentrations. Permeation of drugs is targeted in some cases to body regions close to the action site, where a regional effect is expected, e.g., in the muscles, blood vessels, and articulations. In this way, the term "cutaneous absorption" is properly used to characterize the sum of the amounts of drug that penetrate and permeate the skin (Barry, 2001;El Maghraby, Barry;Willi...

Evaluation of the in vitro Human Skin Percutaneous Absorption of Progesterone in Versabase® Using the Franz Skin Finite Dose Model

“…Inadequate study protocols generate inadequate data; the experimental conditions must be carefully designed taking into account the formulation tested and the physicochemical characteristics of the drug [9]. Preferably, the study protocols should be validated to reduce data variability and to enhance reproducibility [10].…”

“…Animal skin is often employed in these studies due to the limited availability of human skin excised from cadavers or obtained from plastic surgeries; these samples do not always correlate to the human skin absorption as a result of differences in thickness, follicular structure and vascular anatomy, among others [9]. When human skin is used, variables such as the anatomical site, the skin hydration and the age of the person also affect the skin absorption [11].…”

“…Another limitation to consider is the number of the samples used to obtain significant results; it is not always possible to employ as many samples as required for statistical power. Furthermore, in vitro evaluations cannot fully reproduce the complexity of biological systems; when extrapolated, the study results should be considered only a prediction of the in vivo skin absorption [9].…”

Methods to Evaluate Skin Penetration In Vitro

“…In addition to drug penetration testing, the effect of the substance on skin hydration and skin proteins can be observed, e.g., to modify the secondary structure of keratin. Tape stripping can also be used in vitro and in vivo on human and animal skin, as well as on appropriate skin models [15,25,80]. The Organization for Economic Co-operation and Development Test Guideline (OECD TG) 427 describes the use of tape stripping for the removal of upper skin layers and the in vivo penetration of active substances [31], while the OECD TG 428 has been performed with the in vitro application of the method for experiments [32].…”

Engineered Skin Tissue Equivalents for Product Evaluation and Therapeutic Applications

“…An additional testing method is the in vivo DPK method, which uses adhesive tape to strip the stratum corneum layers for analysis of drug penetration . The use of the DPK method has been investigated by the FDA for testing the bioequivalence of topical dermatological products.…”