Novel gastroretentive dosage forms: Evaluation of gastroretentivity and its effect on levodopa absorption in humans

Eytan A. Klausner, Eran Lavy, Miklos Barta, Eva Cserepes, Michael Friedman, Amnon Hoffman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

Purpose. To design novel expandable gastroretentive dosage forms (GRDFs) and evaluate their gastroretentive properties. Then, to assess the pharmacokinetics of levodopa compounded in such a GRDF in healthy volunteers. Methods. Thin (<0.07 cm), large-dimensioned (≥ 5 × 2.1 cm), multi-layer dosage forms (DFs) with different rigid polymeric matrices and mechanical properties were folded into gelatin capsules and were administered to healthy volunteers with a light breakfast. GRDF unfolding and physical integrity were evaluated in vitro and in vivo (by gastroscopy and radiology). The pharmacokinetics of levodopa-GRDF were compared to Sinemet CR® in a crossover design. Results. The combination of rigidity and large dimension of the GRDFs was a decisive parameter to ensure prolonged gastroretentivity (≥ 5 h). Large-dimension DFs lacking rigidity had similar gastroretentivity as a nondisintegrating tablet (10 mm). The GRDFs rapidly unfolded and maintained their mechanical integrity. The absorption phase of levodopa was significantly prolonged following GRDF administration in comparison to Sinemet CR®. Conclusions. The combination of size and rigidity of the novel GRDF enables a significant extension of the absorption phase of a narrow absorption window drug such as levodopa. This approach is an important step toward the implementation of such GRDFs in the clinical setting.

Original languageAmerican English
Pages (from-to)1466-1473
Number of pages8
JournalPharmaceutical Research
Volume20
Issue number9
DOIs
StatePublished - 1 Sep 2003

Keywords

  • Controlled release
  • Drug delivery
  • Gastroretentive
  • Healthy volunteers
  • Levodopa

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