Passive transdermal systems whitepaper incorporating current chemistry, manufacturing and controls (CMC) development principles.

In this whitepaper, the Manufacturing Technical Committee (MTC) of the Product Quality Research Institute has updated the 1997 Transdermal Drug Delivery Systems Scale-Up and Post Approval Change workshop report findings to add important new product development and control principles. Important topics reviewed include ICH harmonization, quality by design, process analytical technologies, product and process validation, improvements to control of critical excipients, and discussion of Food and Drug Administration's Guidance on Residual Drug in Transdermal and Related Drug Delivery Systems as well as current thinking and trends on in vitro-in vivo correlation considerations for transdermal systems.

Transdermal delivery of macromolecules using solid-state biodegradable microstructures.

PURPOSE: The purpose of this work is to demonstrate the feasibility of using a proprietary technology called MicroCor™, based on solid-state, biodegradable microstructures (SSBMS), for transdermal delivery of macromolecules. METHODS: The proteins FITC-BSA (66 kDa) and recombinant protective antigen (rPA; 83 kDa) were incorporated into SSBMS arrays using a mold-based, liquid formulation casting and drying process. Arrays were applied to the skin with a custom applicator and then inspected to assess the extent of microstructure dissolution. In vitro FITC-BSA delivery to human cadaver skin was visualized using light and fluorescence microscopy and quantified by extracting and measuring the fluorescently labeled protein. rPA-containing SSBMS arrays were applied in vivo to Sprague-Dawley rats. The resulting serum IgG response was measured by ELISA and compared with responses elicited from intramuscular (IM) and intradermal (ID) routes of administration. RESULTS: FITC-BSA and rPA SSBMS arrays successfully penetrated the skin. Microstructure dissolution was observed over >95% of the array area and >75% of the microstructure length. FITC-BSA delivery correlated with protein content in the formulations. Antibody titers after transdermal delivery of rPA were comparable or higher than IM and ID titers. CONCLUSIONS: Transdermal delivery of macromolecules can be conveniently and effectively accomplished using the MicroCor technology.

The structure and function of the stratum corneum.

Over the past 150 years the skin's structure and function has been the subject of much investigation by scientists. The stratum corneum (SC), the skin's outermost layer and interface with the outside world is now well recognized as the barrier that prevents unwanted materials from entering, and excessive loss of water from exiting the body. This review summarizes the major advances in our understanding of this formidable membrane. The structure of the SC is outlined as well as techniques to visualize the barrier. The lipid organization and ionic gradients, as well as the metabolic responses and underlying cellular signalling that lead to barrier repair and homeostasis are discussed. Finally, a brief overview of the molecular and genetic factors that determine the development of a competent permeability barrier is provided.