An electro-conductive fluid as a responsive implant for the controlled stimuli-release of diclofenac sodium

Pharm Dev Technol. 2016 Nov;21(7):875-886. doi: 10.3109/10837450.2015.1073742. Epub 2015 Aug 10.

Abstract

The purpose of this study was to develop an electro-responsive co-polymeric (ERP) implantable gel from polyethylene glycol (PEG), sodium polystyrene sulphonate (NaPss), polyvinyl alcohol (PVA), and diethyl acetomidomalonate (DAA) for electro-liberation of the model drug diclofenac sodium. Various physicochemical and physicomechanical characterization tests were undertaken on the synthesized drug-free gel (ERP G1) and drug-loaded gel (ERP G2). The ability of the gel to release diclofenac sodium following electrical stimulation was evaluated using a galvanostat while Molecular Mechanics (MM) simulations were performed to elucidate the experimental mechanisms. A stable electro-active gel exhibiting superior cycling stability was produced with desirable rheological properties, rigidity (BHN = 35.4 N ± 0.33 N/mm2; resilience = 10.91 ± 0.11%), thermal properties (Tg ≈ 70 °C; Tc ≈ 200 °C) and homogeneous morphology. "ON-OFF" pursatile gradual drug release (37-94% from t30 min-t180 min) kinetics was observed upon applying electric stimulation intermittently, indicating that drug release from the gel was electrically controlled. Overall, the galvanometric and MM evaluation ascertained the suitability of the PEG/NaPss/PVA ERP-Gel for application as a subcutaneously injectable drug delivery implant.

Keywords: Diclofenac sodium; electro-conductive fluid; molecular mechanics simulations; stimuli responsive implant; “ON–OFF” pulsatile drug release kinetics.

MeSH terms

  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry*
  • Diclofenac / administration & dosage
  • Diclofenac / chemistry*
  • Drug Delivery Systems / methods
  • Drug Liberation
  • Gels / administration & dosage
  • Gels / chemistry
  • Malonates / chemistry
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Polystyrenes / chemistry
  • Polyvinyl Alcohol / chemistry

Substances

  • Delayed-Action Preparations
  • Gels
  • Malonates
  • Polymers
  • Polystyrenes
  • diethyl acetamidomalonic acid
  • Diclofenac
  • Polyethylene Glycols
  • polystyrene sulfonic acid
  • Polyvinyl Alcohol