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This chapter introduces the routes of administration of therapeutic and diagnostic compounds to the body, the considerations in designing drug delivery systems, and some examples of the innovations that have contributed new controlled delivery products. In addition to the oral route, the most common nonparenteral routes of delivery are topical/transdermal, nasal, pulmonary, ocular, rectal, and vaginal. The parenteral route enables precise dosing for drugs that have a narrow therapeutic index, complete dosing for those with poor oral bioavailability to maintain optimal therapeutic concentrations, ready access in patients with swallowing difficulties, or an unconscious patient, and immediate blood levels of drugs in an emergency. The most common routes used for systemic delivery of a wide range of molecules including biopharmaceuticals, are subcutaneous route, intravenous, and intramuscular route. The chapter provides an overview of the formulation challenges and opportunities offered by the oral route.

Repeated long-term exposure to ultraviolet radiation causes skin aging and increased risk of skin cancer, whereas acute exposure can cause sunburn and significant discomfort. Strategies that have been demonstrated to protect the skin, including the regular use of efficient sunscreens, are heavily promoted by cancer prevention organizations and can provide better health outcomes for individuals and cost savings for health care systems. Consequently, sunscreen actives are present in many cosmetic and personal care products, as well as “beach sunscreen” products. In all cases the advice is to apply liberally, well before expected sun exposure. Sunscreens are used to protect against solar ultraviolet radiation. Sunscreen products are typically formulated to provide high skin substantivity. It is therefore important that in vitro experiments are designed to assess both permeation through the skin and penetration into/retention in the skin over the time course of topical application.

Refereed/Peer-reviewed Epithelial surfaces protect exposed tissues in the body against intrusion of foreign materials, including xenobiotics, pollen and microbiota. The relative permeability of the various epithelia reflects their extent of exposure to the external environment and is in the ranking: intestinal≈ nasal ≥ bronchial ≥ tracheal > vaginal ≥ rectal > blood-perilymph barrier (otic), corneal > buccal > skin. Each epithelium also varies in their morphology, biochemistry, physiology, immunology and external fluid in line with their function. Each epithelium is also used as drug delivery sites to treat local conditions and, in some cases, for systemic delivery. The associated delivery systems have had to evolve to enable the delivery of larger drugs and biologicals, such as peptides, proteins, antibodies and biologicals and now include a range of physical, chemical, electrical, light, sound and other enhancement technologies. In addition, the quality-by-design approach to product regulation and the growth of generic products have also fostered advancement in epithelial drug delivery systems.

It is critical to develop an effective understanding of the interaction between the drug, delivery system and skin in order to predict and assess skin penetration and permeation. Experimental models for the assessment of topical and transdermal delivery systems must permit evaluation of these complex interactions. Whilst in the past, animal models were commonly used, recent regulatory guidelines, based on 3R principles (refinement, reduction, replacement), encourage the rational use of animals. Alternative methods have been proposed for use in the development of topical and transdermal delivery systems which are often used in combination. We will review the current state of the art in alternative methods for topical and transdermal delivery systems development, including technologies that can assist in the characterization of skin penetration/permeation studies.