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Topical drug delivery: History, percutaneous absorption, and product development

Journal

ADVANCED DRUG DELIVERY REVIEWS
Volume 177, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.addr.2021.113929

Keywords

Topical drug delivery; Skin and its appendages; History; Mechanism; Percutaneous absorption; Product development; QSPR; PBPK; IVPT; Finite dose; Clearance; Bioequivalence; Heterogeneity; Consumer behavior

Funding

  1. Australian NHMRC [1107356, APP1049906]
  2. Australian ARC [DP120104792]
  3. US FDA [U01FD006700, 1U01FD006496-01, U01FD006522, 1U01FD005226-01, 1U01FD005232-01]
  4. Australian Government Research Training Program (RTP) Scholarship
  5. National Health and Medical Research Council of Australia [1107356] Funding Source: NHMRC

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Topical drug delivery has evolved from simple potions to sophisticated delivery systems based on mechanistic understanding of drug-product-skin interactions. Insights from QSPR, molecular dynamics simulations, and PBPK have provided valuable information. Currently, generic products dominate the market.
Topical products, widely used to manage skin conditions, have evolved from simple potions to sophisticated delivery systems. Their development has been facilitated by advances in percutaneous absorption and product design based on an increasingly mechanistic understanding of drug-product-skin interactions, associated experiments, and a quality-by-design framework. Topical drug delivery involves drug transport from a product on the skin to a local target site and then clearance by diffusion, metabolism, and the dermal circulation to the rest of the body and deeper tissues. Insights have been provided by Quantitative Structure Permeability Relationships (QSPR), molecular dynamics simulations, and dermal Physiologically Based PharmacoKinetics (PBPK). Currently, generic product equivalents of reference listed products dominate the topical delivery market. There is an increasing regulatory interest in understanding topical product delivery behavior under 'in use' conditions and predicting in vivo response for population variations in skin barrier function and response using in silico and in vitro findings. (c) 2021 Elsevier B.V. All rights reserved.

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