Back to Journals » Journal of Pain Research » Volume 10

Bottlenecks in the development of topical analgesics: molecule, formulation, dose-finding, and phase III design

Authors Keppel Hesselink JM, Kopsky DJ, Stahl SM

Received 1 January 2017

Accepted for publication 13 February 2017

Published 20 March 2017 Volume 2017:10 Pages 635—641

DOI https://doi.org/10.2147/JPR.S131434

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Michael Schatman

Jan M Keppel Hesselink,1 David J Kopsky,2 Stephen M Stahl3

1Institute Neuropathic Pain, Bosch en Duin, the Netherlands; 2Institute Neuropathic Pain, Amsterdam, the Netherlands; 3University of California San Diego, La Jolla, CA, USA

Abstract: Topical analgesics can be defined as topical formulations containing analgesics or co-analgesics. Since 2000, interest in such formulations has been on the rise. There are, however, four critical issues in the research and development phases of topical analgesics: 1) The selection of the active pharmaceutical ingredient. Analgesics and co-analgesics differ greatly in their mechanism of action, and it is required to find the most optimal fit between such mechanisms of action and the pathogenesis of the targeted (neuropathic) pain. 2) Issues concerning the optimized formulation. For relevant clinical efficacy, specific characteristics for the selected vehicle (eg, cream base or gel base) are required, depending on the physicochemical characteristics of the active pharmaceutical ingredient(s) to be delivered. 3) Well-designed phase II dose-finding studies are required, and, unfortunately, such trials are missing. In fact, we will demonstrate that underdosing is one of the major hurdles to detect meaningful and statistically relevant clinical effects of topical analgesics. 4) Selection of clinical end points and innovatively designed phase III trials. End point selection can make or break a trial. For instance, to include numbness together with tingling as a composite end point for neuropathic pain seems stretching the therapeutic impact of an analgesic too far. Given the fast onset of action of topical analgesics (usually within 30 minutes), enrichment designs might enhance the chances for success, as the placebo response might decrease. Topical analgesics may become promising inroads for the treatment of neuropathic pain, once sufficient attention is given to these four key aspects.

Keywords: topical, analgesics, cream, gel, dose-finding, formulation, ketamine, amitriptyline, baclofen, enrichment

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Other articles by this author:

Topical phenytoin for the treatment of neuropathic pain

Kopsky DJ, Keppel Hesselink JM

Journal of Pain Research 2017, 10:469-473

Published Date: 27 February 2017