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

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...

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Main Authors: Hellen Windolf, Rebecca Chamberlain, Jörg Breitkreutz, Julian Quodbach
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/14/5/931
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author Hellen Windolf
Rebecca Chamberlain
Jörg Breitkreutz
Julian Quodbach
author_facet Hellen Windolf
Rebecca Chamberlain
Jörg Breitkreutz
Julian Quodbach
author_sort Hellen Windolf
collection DOAJ
description 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 (f<sub>2</sub> > 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.
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spelling doaj.art-a743e5e4d30b4945ac65bb74f3fb2a072023-11-23T12:36:44ZengMDPI AGPharmaceutics1999-49232022-04-0114593110.3390/pharmaceutics140509313D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized TherapyHellen Windolf0Rebecca Chamberlain1Jörg Breitkreutz2Julian Quodbach3Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, GermanyInstitute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, GermanyInstitute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, GermanyInstitute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitätsstr. 1, 40225 Düsseldorf, GermanyTherapy 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 (f<sub>2</sub> > 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.https://www.mdpi.com/1999-4923/14/5/931FDM 3D printingpolypillMorbus Parkinsonpersonalized medicineadditive manufacturinggastro retentive drug delivery
spellingShingle Hellen Windolf
Rebecca Chamberlain
Jörg Breitkreutz
Julian Quodbach
3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy
Pharmaceutics
FDM 3D printing
polypill
Morbus Parkinson
personalized medicine
additive manufacturing
gastro retentive drug delivery
title 3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy
title_full 3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy
title_fullStr 3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy
title_full_unstemmed 3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy
title_short 3D Printed Mini-Floating-Polypill for Parkinson’s Disease: Combination of Levodopa, Benserazide, and Pramipexole in Various Dosing for Personalized Therapy
title_sort 3d printed mini floating polypill for parkinson s disease combination of levodopa benserazide and pramipexole in various dosing for personalized therapy
topic FDM 3D printing
polypill
Morbus Parkinson
personalized medicine
additive manufacturing
gastro retentive drug delivery
url https://www.mdpi.com/1999-4923/14/5/931
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