Kawanami, Toshio, La Bonte, Laura, Amin, Jakal, Thibodeaux, Stefan, Lee, Cameron, Argintaru, Andreea and Adams, Christopher (2020) A novel diclofenac-hydrogel conjugate system for intraarticular sustained release: Development of 2-pyridylamino-substituted 1-phenylethanol (PAPE) and its derivatives as tunable traceless linkers. International journal of pharmaceutics, 585. p. 119519. ISSN 03785173

Abstract

A local sustained-release drug delivery system, or depot, for intra-articular injection offers the opportunity to release a therapeutic agent directly to the joint with limited need for reinjection. A successful system would provide more consistent efficacy and minimize systemic side effects. In this paper, we explore the potential use of diclofenac, a non-steroidal anti-inflammatory drug, for use in a polymer-conjugate depot system. During the course of our exploration it was determined that “conventional ester” conjugates of diclofenac were not appropriate as upon incubation in buffer (pH 7.4) or in bovine synovial fluid, a considerable amount of undesired diclofenac-lactam was released. Thus we developed a novel linker system for diclofenac in order to minimize the production of the lactam. This new linker enables a diclofenac conjugate system with tunable release rates and minimizes the production of undesired lactam side-products.

Item Type:	Article
Date Deposited:	11 Jul 2020 00:45
Last Modified:	11 Jul 2020 00:45
URI:	https://oak.novartis.com/id/eprint/33445