Poly(caprolactone)-based subcutaneous implant for sustained delivery of levothyroxine

Sarah A Stewart, Juan Domínguez-Robles, Emilia Utomo, Camila J Picco, Francesca Corduas, Elena Mancuso, Muh Nur Amir, Muh Akbar Bahar, Sumarheni Sumarheni, Ryan F Donnelly, Andi Dian Permana, Eneko Larrañeta

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

This work aimed to develop a subcutaneous implant for prolonged delivery of LEVO to treat hypothyroidism. This could overcome challenges with patient compliance and co-administration and could improve treatment of this condition. For this purpose, implants were produced by solvent casting mixtures of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG) and LEVO sodium. These implants contained mixtures of PCL of differing molecular weight, PEG and different LEVO sodium loadings (20% or 40% w/w). SEM images confirmed that the drug was evenly dispersed throughout the implant. In vitro release rates ranging from 28.37 ± 1.19 – 78.21 ± 19.93 µg/day and 47.39 ± 8.76 – 98.92 ± 4.27 µg/day were achieved for formulations containing 20% and 40% w/w drug loading, respectively. Implants containing higher amounts of low molecular weight PCL and 40% w/w of LEVO showed release profiles governed by zero order kinetics. On the other hand, implants containing higher amounts of high molecular weight PCL showed a release mechanism governed by Fickian diffusion. Finally, two representative formulations were tested in vivo. These implants were capable of providing detectable LEVO levels in plasma during the entire duration of the experiments (4 weeks) with LEVO plasma levels ranging between 5 and 20 ng/mL.

Original languageEnglish
Article number121011
Number of pages10
JournalInternational Journal of Pharmaceutics
Volume607
Early online date13 Aug 2021
DOIs
Publication statusPublished - 25 Sep 2021

Keywords

  • Hypothyroidism
  • Implantable Devices
  • Levothyroxine
  • Poly(caprolactone)
  • Sustained release

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