title: Evaluation of osmotic effects on coated pellets using a mechanistic model.
abstract: The aim of this study was to develop a simple experimental methodology and to develop a mechanistic model to characterize the release mechanism from pellets developing cracks during the release process with special focus on osmotic effects. The release of remoxipride from pellets coated with an ethyl cellulose film was chosen as a case study. Dose release experiments at different bulk osmotic pressures revealed that the release process was mainly osmotically driven. The model was used to calculate the solvent permeability of the coating, 1.1 x 10(-10)m(2)h(-1)MPa(-1). The model was validated by release experiments using similar pellets having different coating thicknesses. The effective diffusion coefficient of remoxipride in the coating was also calculated and found to be 1.7 x 10(-10)m(2)h(-1). A series of experiments was performed in which the osmotic pressure of the receiving solution was changed during the experiment. From the results of these experiments, the area of the cracks in the film, formed by the hydrostatic pressure built up inside the pellets, was estimated to be 3.5 x 10(-5)m(2)/m(2) coating. It could also be deduced that the solvent permeability of the coating film was affected by swelling in the same way at different osmotic pressures.
authors.affiliation: Department of Chemical Engineering, Lund University, PO Box 124, SE-221 00 Lund, Sweden. mariagraziam@chemeng.lth.se
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Marucci
authors.forename: Gert
authors.initials: G
authors.lastname: Ragnarsson
authors.forename: Anders
authors.initials: A
authors.lastname: Axelsson
mesh_terms: D000465:Algorithms; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D004058:Diffusion; D005947:Glucose / Q000737:chemistry; D008956:Models, Chemical; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D017330:Remoxipride / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013608:Tablets, Enteric-Coated / Q000737:chemistry*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D002951:Citrates; D004364:Pharmaceutical Preparations; D013608:Tablets, Enteric-Coated; D017330:Remoxipride; D014867:Water; C013517:ethyl cellulose; C023001:ethyl citrate; D002482:Cellulose; D005947:Glucose