Novel levodopa gastroretentive dosage form: In-vivo evaluation in dogs

Eytan A. Klausner, Sara Eyal, Eran Lavy, Michael Friedman, Amnon Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

96 Scopus citations

Abstract

Due to its narrow absorption window, levodopa has to be administered continuously to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a controlled release (CR) gastroretentive dosage form (GRDF). The aim of this work was to develop a novel GRDF, based on unfolding polymeric membranes, that combines extended dimensions with high rigidity, and to examine the pharmacokinetics of levodopa compounded in the GRDF. Levodopa CR-GRDFs were administered to beagle dogs pretreated with carbidopa. The CR-GRDF location in the gastrointestinal tract was determined by X-ray, and serial blood samples were collected and assayed for levodopa. Optimization of the pharmacokinetic profile of levodopa from the CR-GRDFs was carried out based on the in-vitro in-vivo correlation following modifications of the release rates (adjusted by various membrane thicknesses) and drug loads. The successful CR-GRDF maintained therapeutic levodopa concentrations (>500 ng ml-1) over 9 h. In comparison to non-gastroretentive CR-particles and oral solution, mean absorption time was significantly extended. These outcomes demonstrate that the CR-GRDF may be used to improve levodopa therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input.

Original languageAmerican English
Pages (from-to)117-126
Number of pages10
JournalJournal of Controlled Release
Volume88
Issue number1
DOIs
StatePublished - 14 Feb 2003

Bibliographical note

Funding Information:
This paper is a part of Eytan Klausner’s Ph.D. dissertation. We thank Dr. Josh Backon for constructive comments. This study was supported by the Ministry of Science of Israel and Intec Pharmaceuticals (2000) Ltd. Prof. Amnon Hoffman and Prof. Michael Friedman are affiliated with the David R. Bloom Center for Pharmacy.

Keywords

  • Controlled release
  • Gastroretentive
  • Levodopa
  • Oral absorption
  • Pharmacokinetics

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