Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease

Abstract When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at...

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Main Authors: William L. Murch, John Spiridigliozzi, Adam Heller, Ephraim Heller
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-024-78145-4
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author William L. Murch
John Spiridigliozzi
Adam Heller
Ephraim Heller
author_facet William L. Murch
John Spiridigliozzi
Adam Heller
Ephraim Heller
author_sort William L. Murch
collection DOAJ
description Abstract When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at daily doses exceeding 100 mg has, for many years, been considered an insurmountable challenge. We show that over 1200 mg/day of 4:1 levodopa-carbidopa (LD-CD) can be non-invasively and continuously extruded when formulated as a semisolid paste, loaded with 63%w/w of the solid drugs. The drug delivery system comprises a reusable orthodontic retainer with a co-molded pocket into which the patient inserts after each meal a new 1 mL propellant-driven, prefilled, disposable, drug delivery extruder. The paste is delivered to the lingual side of the teeth where it is mixed with saliva and swallowed. As reported elsewhere, a 15-day, 16 patient open label clinical trial of the drug delivery system continuously extruding LD-CD paste significantly reduces the variability of the plasma LD concentration and alleviates symptoms of advanced Parkinson’s disease (PD) as compared to LD-CD tablets.
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spelling doaj-art-27bf1ac536ef48e4a5f03d76f1e47a002025-08-20T02:13:55ZengNature PortfolioScientific Reports2045-23222024-11-011411910.1038/s41598-024-78145-4Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s diseaseWilliam L. Murch0John Spiridigliozzi1Adam Heller2Ephraim Heller3synAgile CorporationsynAgile CorporationsynAgile CorporationsynAgile CorporationAbstract When short plasma half-life drugs act only briefly, they require frequent or continuous administration. We report the engineering of a non-invasive oral drug delivery system for long-term, continuous administration of these drugs. Their non-invasive, long-term, continuous administration at daily doses exceeding 100 mg has, for many years, been considered an insurmountable challenge. We show that over 1200 mg/day of 4:1 levodopa-carbidopa (LD-CD) can be non-invasively and continuously extruded when formulated as a semisolid paste, loaded with 63%w/w of the solid drugs. The drug delivery system comprises a reusable orthodontic retainer with a co-molded pocket into which the patient inserts after each meal a new 1 mL propellant-driven, prefilled, disposable, drug delivery extruder. The paste is delivered to the lingual side of the teeth where it is mixed with saliva and swallowed. As reported elsewhere, a 15-day, 16 patient open label clinical trial of the drug delivery system continuously extruding LD-CD paste significantly reduces the variability of the plasma LD concentration and alleviates symptoms of advanced Parkinson’s disease (PD) as compared to LD-CD tablets.https://doi.org/10.1038/s41598-024-78145-4
spellingShingle William L. Murch
John Spiridigliozzi
Adam Heller
Ephraim Heller
Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
Scientific Reports
title Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
title_full Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
title_fullStr Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
title_full_unstemmed Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
title_short Non-invasive, continuous oral delivery of solid levodopa-carbidopa for management of Parkinson’s disease
title_sort non invasive continuous oral delivery of solid levodopa carbidopa for management of parkinson s disease
url https://doi.org/10.1038/s41598-024-78145-4
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