title: Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.
abstract: This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.
authors.affiliation: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles, Campus de la Plaine, CP 207, Boulevard du Triomphe, Brussels 1050, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Goole
authors.forename: F
authors.initials: F
authors.lastname: Vanderbist
authors.forename: K
authors.initials: K
authors.lastname: Amighi
mesh_terms: D000268:Adhesiveness; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007980:Levodopa / Q000008:administration & dosage* / Q000737:chemistry; D008747:Methylcellulose / Q000737:chemistry*; D012995:Solubility; D013607:Tablets / Q000737:chemistry*
chemical_list: D000978:Antiparkinson Agents; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D007980:Levodopa; D008747:Methylcellulose