Novel gastroretentive dosage forms: evaluation of gastroretentivity and its effect on levodopa absorption in humans.
OBJECTIVE
To design novel expandable gastroretentive dosage form (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 (> or = 5 x 2.1 cm), multi layer dosage forms (DFs) with different rigid polymeric matrices an mechanical properties were folded into gelatin capsules and wer 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 (> or = 5 h). Large-dimension DFs lacking rigidity had similar gastroretentivity as a nondisintegrating tablet (10 mm). The GRDF 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.
Klausner
Eytan A
EA
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Lavy
Eran
E
Barta
Miklos
M
Cserepes
Eva
E
Friedman
Michael
M
Hoffman
Amnon
A
D000284:Administration, Oral; D000328:Adult; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D007980:Levodopa / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D012995:Solubility; D013270:Stomach / Q000502:physiology; D013997:Time Factors
D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D007980:Levodopa