Laboratory Testing Blog

Practically, in vivo skin absorption measurement studies are rare due to ethical, economical, and analytical concerns. Therefore, a shift in focus has been made to developing and validating alternative in vitro test methods. The diversity of existing in vitro and in vivo techniques shows the difficulties of comparing results between different methods, species, ages, as well as healthy and diseased skin.

Transdermal patches are designed to slowly deliver the drug substances through the intact skin, resulting in a prolonged and adequately constant systemic absorption rate.  The rate limiting step for systemic absorption of the drug substance is usually the absorption through the skin.  Absorption may also be limited by incorporating or dissolving the drug substance in a semisolid reservoir with a membrane to control the release and the diffusion of the drug substance(s) from the transdermal patch.  A transdermal patch can also be formulated combining both drug delivery principles as the means of controlling drug delivery to the surface of the skin.

Quality control testing of human skin models is a crucial element to consider when performing in vitro percutaneous absorption studies.  This fact is reflected in various toxicological regulations such as the European Union's Scientific Committee on Consumer Safety (SCCS) test guidelines for for the in vitro assessment of dermal absorption of cosmetic ingredients.

In the European Union and some other countries, it is general practice while performing in vitro skin penetration studies, to exclude the amount of Test article that was found in the first (upper) two tape strips at study completion both in vitro and in vivo.

Driven by regulatory requirements, skin penetration and absorption studies are becoming essential for safety and efficacy evaluation of test substances or formulations.  In vivo, substances topically applied onto the skin surface can diffuse into and penetrate through the skin using three distinct pathways, namely the intercellular and the transcellular route across the stratum corneum as well as the route along the skin appendages (hair follicles and sweat glands).  Both the percutaneous penetration and the absorption into different skin compartments of topically applied test substances can be evaluated by using a Franz diffusion cell apparatus.

Biodegradable microparticles formulated using biodegradable polymers, such as polylactide (PLA), poly (lactideco- glycolide) (PLGA) (1Y6), gelatin (7Y9) and albumin have been used as carriers for small molecules and biologically active peptides and proteins.  In addition to being biodegradable, other advantages include reduced frequency of administration, enhanced patient compliance, sustained drug release, reduced dosage and less systemic side effects.  PLA and PLGA have been approved for human use by the United States Food and Drug Administration (US FDA) as surgical sutures, implantable devices and other drug delivery systems.

The purpose of dermal absorption studies of topical formulations is to obtain quantitative information on the amounts that can enter, under in-use conditions, into the systemic compartment.  These quantities can then be taken into consideration to calculate a safety factor.  Justification for the use of in vitro dermal absorption studies on isolated skin is based on the fact that the epidermis, in particular the stratum corneum, forms the principal in vivo barrier of the skin against the penetration and uptake of xenobiotics in the body.

The in vitro percutaneous absorption method has been described in detail in several publications and previously in our blog posts and whitepapers.  One interesting question that has arisen recently is how to provide data for skin integrity testing.

Drugs have been administered nasally for therapeutic and recreational purposes since ancient times.  Psychotropic drugs and hallucinogens were snuffed for these purposes by the South American Indians, and this practice is currently widespread among abusers of cocaine and heroin.

Although FDA does not officially require it yet, the human cadaver skin model is a powerful and sensitive tool by which to accurately quantitate a semisold drug’s rate of percutaneous absorption.  This has application within multiple areas of the semisolid drug development process.  The area of greatest application historically has been in preclinical development, where it is used to screen and select the optimum formulation for further development.