Development of Polycaprolactone-Based metronidazole matrices for intravaginal extended drug delivery using a mechanochemically prepared therapeutic deep eutectic system

Shu Li*, Alice Culkin, David S. Jones, Gavin P. Andrews

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The engineering of crystalline multi-component drug systems, including cocrystals and salts, is now an established method of modifying the physicochemical properties and dissolution behaviour of an active ingredient. Remarkably, liquid drug systems, including therapeutic ionic liquids and therapeutic deep eutectic solvents (THEDES), remain largely unexplored as an untapped reservoir for drug modification. In this work, the formation of a THEDES containing metronidazole (MET), the preferred first-line treatment for bacterial vaginosis (BV), was explored. The formed THEDES was evaluated for its dissolution behaviour from a simple polycaprolactone (PCL) matrix, in order to achieve an extended release, balanced with an appropriate onset of action, hence offering improved MET intravaginal application. To minimise handling of the liquid THEDES, an end-to-end continuous process that enables feeding of the raw materials in their respective solid forms, and collection of a solidified final formulation is presented. The concurrent THEDES formation and formulation were carried out using a bench scale (approx. 10 g) twin-screw hot melt extruder. The chosen parent reagents have shown sufficiently strong reactivity and resulted in successful and complete conversion to THEDES while in the presence of PCL, during the extrusion process. The formulated THEDES-PCL matrix exhibited significantly improved onset of drug release followed by a controlled delivery of MET over a total 7-day period in SVF, proving itself as a viable alternative to oral therapy.

Original languageEnglish
Article number120071
JournalInternational Journal of Pharmaceutics
Volume593
Early online date25 Nov 2020
DOIs
Publication statusPublished - 25 Jan 2021

Bibliographical note

Publisher Copyright:
© 2020 Elsevier B.V.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

Keywords

  • Antimicrobial
  • Extended release
  • Hot melt reactive extrusion
  • Intravaginal delivery
  • Mechanochemical preparation
  • Metronidazole
  • Multi-component pharmaceutical materials
  • Polycaprolactone
  • Therapeutic deep eutectic

ASJC Scopus subject areas

  • Pharmaceutical Science

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