Formulation considerations for the development of medications with abuse potential.
The availability of increasingly sophisticated drug formulations and delivery devices has created new opportunities in drug development. These newer approaches can result in improved drug bioavailability, or they can alter key pharmacokinetic parameters in such a way as to decrease dosing interval, decrease variability, or blunt maximal concentrations that are associated with adverse events of particular concern. Special formulations or devices can also provide for easier or more convenient dosing in subpopulations of interest, such as children or the elderly. Although the key principles of abuse potential assessment and the underlying neurochemistry and pharmacology are relatively well understood, evaluation of the influences of drug formulation have received much less study. Because dose and formulation - and even the therapeutic indication - are refined over the course of development, it is usually difficult to conduct more than a cursory evaluation of the influence of formulation on the underlying abuse potential of the active pharmaceutical ingredient. Industrial sponsors would benefit from further research in areas of formulation science and pharmacokinetics that would improve the predictability of prescription drug abuse. In particular, validation of new pharmacokinetic parameters and standardization of methods to understand the consequences of product tampering could assist in gaining a better assessment of risk for controlled release formulations. Such methods could apply not only to innovator products, but also to those wishing to develop generic versions with similar pharmaceutical performance. This article proposes several factors that may be of use to industrial sponsors in making formulation choices for drugs with the potential for abuse.
Mansbach
Robert S
RS
Departments of Regulatory Affairs and Pharmaceutical Development, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA. rmansbac@prdus.jnj.com
Moore
Richard A
RA
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions; D004335:Drug and Narcotic Control / Q000331:legislation & jurisprudence / Q000379:methods*; D006801:Humans; D019966:Substance-Related Disorders / Q000517:prevention & control*; D014481:United States