Journal of Controlled Release 67 (2000) 293–307 www.elsevier.com / locate / jconrel In vitro studies and modeling of a controlled-release device for root canal therapy a a a a, b b * J. Huang , H.-L. Wong ,Y. Zhou , X.Y. Wu , H. Grad , R. Komorowski , b S. Friedman a Faculty of Pharmacy, University of Toronto, Toronto, Canada M5S 2S2 b Faculty of Dentistry, University of Toronto, Toronto, Canada M5S 2S2 Received 21 October 1999; accepted 26 January 2000 Abstract Endodontic disease is caused primarily by bacteria that interact with periradicular host tissues. Therefore, treatment of endodontic disease aims at the exclusion of bacteria from the root canal system. This work focused on in vitro studies and modeling of a controlled-release device for delivering antimicrobial agents in root canals. A cylindrical, needle-shaped device was prepared consisting of a matrix core and a polymer coating, loaded with 30–45% chlorhexidine (CHX). The composition of the core, a blend of water-permeable polymers, and the thickness of the coating were tailored to impart various release rates. A relatively steady release rate for over 40 days after an initial burst was achieved using a formulation for long-term release, which is desirable for establishing and maintaining the necessary therapeutic levels. Mathematical models were developed for both in vitro and in vivo drug release into a liquid of limited volume, taking into account a moving boundary of the dispersed drug and a time-dependent boundary condition. A concentration-dependent effective diffusion coefficient was used to count increased porosity as the solid drug had dissolved. The finite element method and computer programs were applied to solve the differential equations and predict the in vitro and in vivo release kinetics. The model prediction agreed well with the in vitro experimental data and provided guidance for designing the device for in vivo release in root canals. The result of in vitro antimicrobial tests, performed using a bovine tooth model, suggested that the device was effective in reducing growth of microbes.  2000 Elsevier Science B.V. All rights reserved. Keywords: Controlled-release device; Dental root canal; Antimicrobial; Modeling; Finite element method; Moving boundary; In vitro and simulated in vivo 1. Introduction tion of the dental pulp tissue and the bone supporting the tooth, which are affected by oral microorganisms Endodontic disease, such as pulpitis or periradicu- invading the tooth. It is a very common occurrence lar periodontitis, is caused by infection or inflamma- that affects 70% of the population in countries with well-developed dental care modes, and by estimate, over 95% of the population in other parts of the *Corresponding author. 19 Russell Street, Toronto, Ontario, world; and it is one of the major causes of tooth loss Canada M5S 2S2. Tel.: 11-416-978-5272; fax: 11-416-978- in these populations. 8511. E-mail address: xywu@phm.utoronto.ca (X.Y. Wu) Endodontic disease is an all-inclusive term for a 0168-3659 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0168-3659(00)00225-X