Ingo Alberti

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described.

Transdermal gels are designed to deliver sustained drug amounts, resulting in systemically consistent levels. They represent an improvement compared with transdermal delivery by patches because they offer more dosage flexibility, less irritation potential and a better cosmetic appearance. Advanced Transdermal Delivery™ (ATD™) gel technology was developed in order to provide enhanced passive skin permeation of various active drugs for the treatment of many conditions, including hypogonadism, female sexual dysfunction, postmenopausal symptoms, overactive bladder and anxiety. The technology consists of a combination of solvent systems and permeation enhancers enabling systemic drug delivery, and is covered by many patents. Pharmaceutical development of formulations based on the technology allowed optimisation of physicochemical parameters (rheological profile, pH) as well as skin permeation properties (type and concentration of permeation enhancers, thermodynamic activity of the drug). This gel technology ha...

We present a method to determine the cutaneous bioavailability and hence to evaluate the bioequivalence of topically applied drugs in vivo. The procedure uses serial tape-stripping and transepidermal water loss measurements to quantify the thickness of the removed stratum corneum (SC) and to determine the intact membrane thickness. Following tape-stripping, the drug is extracted from the tapes and assayed, e.g., by HPLC. This provides a drug concentration profile as a function of the normalized position within the SC. The data are fitted to a solution of Fick’s second law of diffusion in order to calculate characteristic membrane transport parameters. Integration of the concentration profile over the entire SC thickness, that is, the ‘area-under-the-curve’, provides a measure of the cutaneous bioavailability and hence can be used to assess the bioequivalence of topically applied drugs.