Prodrugs: Topical and Ocular Drug Delivery

Abstract

Prodrugs are reversible chemical derivatives that are hydrolyzed to release the active drug in an absorbing tissue or organ. This approach represents only a small, but significant, part of drug delivery and there is only one commercial product, Propine (Allergan Pharmaceuticals, Irvine, Calif; dipivalyl epinephrine) that uses this concept in the eye. Nevertheless, prodrugs have considerable potential to improve drug stability and/or membrane permeability and, as such, can dramatically increase the fraction of dose absorbed, the rate and extent of metabolism, and the fraction of dose reaching the biophase from the pool of drug in the surrounding fluid or tissue. These advantages are often offset by higher manufacturing and development costs and greater difficulty in securing US Food and Drug Administration approval. This short text, consisting of seven chapters, deals primarily with percutaneous absorption; five of seven chapters are devoted to prodrugs and the skin, one chapter deals with prediction