3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy

Hellen Windolf, Rebecca Chamberlain, Jörg Breitkreutz, Julian Quodbach*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Therapy for Parkinson’s disease is quite challenging. Numerous drugs are available for symptomatic treatment, and levodopa (LD), in combination with a dopa decarboxylase inhibitor (e.g., benserazide (BZ)), has been the drug of choice for years. As the disease progresses, therapy must be supplemented with a dopamine agonist (e.g., pramipexole (PDM)). Side effects increase, as do the required dose and dosing intervals. For these specific requirements of drug therapy, the 3D printing method fused deposition modelling (FDM) was applied in this study for personalized therapy. Hot melt extrusion was utilized to produce two different compositions into filaments: PDM and polyvinyl alcohol for rapid drug release and a fixed combination of LD/BZ (4:1) in an ethylene-vinyl acetate copolymer matrix for prolonged drug release. Since LD is absorbed in the upper gastrointestinal tract, a formulation that floats in gastric fluid was desired to prolong API absorption. Using the FDM 3D printing process, different polypill geometries were printed from both filaments, with variable dosages. Dosage forms with 15–180 mg LD could be printed, showing similar release rates (f2 > 50). In addition, a mini drug delivery dosage form was printed that released 75% LD/BZ within 750 min and could be used as a gastric retentive drug delivery system due to the floating properties of the composition. The floating mini-polypill was designed to accommodate patients’ swallowing difficulties and to allow for individualized dosing with an API release over a longer period of time.

Original languageEnglish
Article number931
Pages (from-to)1-22
Number of pages22
JournalPharmaceutics
Volume14
Issue number5
DOIs
Publication statusPublished - 25 Apr 2022

Bibliographical note

Funding Information:
Acknowledgments: The authors want to thank Alessandro Guiseppe Elia and Thomas Kipping for the VCM platelet preparation and Andrea Michel for density measurements. We also thank Merck KGaA and TER Chemicals for providing large quantities of PVA and EVA. This work is associated and funded by the Bundesministerium für Bildung und Forschung-Projekt ‘ProMat Leben-Polymere’ ‘PolyPrint’ (Project no.: 13XP5064B).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Funding

Acknowledgments: The authors want to thank Alessandro Guiseppe Elia and Thomas Kipping for the VCM platelet preparation and Andrea Michel for density measurements. We also thank Merck KGaA and TER Chemicals for providing large quantities of PVA and EVA. This work is associated and funded by the Bundesministerium für Bildung und Forschung-Projekt ‘ProMat Leben-Polymere’ ‘PolyPrint’ (Project no.: 13XP5064B).

Keywords

  • additive manufacturing
  • FDM 3D printing
  • gastro retentive drug delivery
  • Morbus Parkinson
  • personalized medicine
  • polypill

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