Alternate routes of administration

Abstract

Patients, caregivers, payers, drug developers, and the continually evolving standard of care all play a critical role in shaping the drug product and formulation requirements to better meet unmet medical needs of patients. A significant area of growth in recent years has been in the non-oral route of administration (alternate route and injectable route of administration, RoA). The use of drug products for alternate route of administration or the use of drug-device combination products offers an opportunity to enable a product in situations where there are significant oral challenges, such as extensive gastrointestinal metabolism, low oral bioavailability, suboptimal oral PK, local gastrointestinal toxicity, or other adverse reactions. Additionally, drug-device combination products (both injectable and non-injectable for alternate route products) present an opportunity to consider an enhanced product that improves patient compliance and increases treatment options to manage diseases. In this chapter, alternate routes of administration such as intranasal, inhalation, buccal/sublingual, and transdermal approaches for delivery of drug candidates to systemic molecular targets are discussed. The rationale for each route of administration, including their strengths and limitations, drug molecule developability criteria, and recommended preclinical testing experiments to enable such products, is reviewed. There has been a steady trend over the past decade in which self-administration has become more and more prevalent among patients. As a result, devices are being developed that incorporate more patient requirements, such as portability, intuitiveness, ease of use, and other human factor considerations. In addition, with the growth of mobile health applications, devices are becoming more connected with mobile devices, enabling better patient compliance with treatment regimens and advancement in standards of care. Product trends and recent advances are outlined in this chapter together with strategies to consider for clinical testing.