Novel Gastroretentive Dosage Forms: Evaluation of Gastroretentivity and Its Effect on Levodopa Absorption in Humans |
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Authors: | Klausner Eytan A. Lavy Eran Barta Miklos Cserepes Eva Friedman Michael Hoffman Amnon |
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Affiliation: | (1) Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, 91120, Israel;(2) Clinical Sciences Department, The School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, 76100, Israel;(3) Department of Radiology, The National Medical Center, Budapest, 1135, Hungary |
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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), multilayer 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. |
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Keywords: | drug delivery controlled release gastroretentive healthy volunteers levodopa |
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