title: Osmotic pumping release from ethyl-hydroxypropyl-cellulose-coated pellets: a new mechanistic model.
abstract: A new mechanistic model of drug release by osmotic pumping and diffusion from pellets coated with a semipermeable film developing pores created by the leaching of water-soluble compounds initially present in the coating, has been developed. The model describes dynamically all the main processes occurring during release, i.e. the inflow of solvent driven by the difference in osmotic pressure across the coating film, dissolution of the drug, swelling of the pellet due to mass accumulation, the build-up of hydrostatic pressure inside the pellet, and the outflow of the dissolved drug through the pores. The model was validated by comparison with the release profile of single metoprolol succinate pellets coated with a film made of ethyl cellulose and hydroxypropyl cellulose (80:20). This system was chosen as it was shown that the release mechanism was osmotic pumping, and that the release occurred through small pores created in the coating by hydroxypropyl cellulose leaching. Insight into the release process was obtained via dose release experiments performed at different osmotic pressures of the release medium, single-pellet release experiments, and a study of the coating before and after immersion in the release medium using scanning electron microscopy. The good agreement found between the predicted release and the experimental data confirmed the validity of the model and its prediction capacity. The model can be used to calculate important variables, e.g. the drug concentration profile in a pore and the pressure build-up inside the pellet.
authors.affiliation: Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden. mariagrazia.marucci@astrazeneca.com
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Marucci
authors.forename: Gert
authors.initials: G
authors.lastname: Ragnarsson
authors.forename: Bernt
authors.initials: B
authors.lastname: Nilsson
authors.forename: Anders
authors.initials: A
authors.lastname: Axelsson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D004058:Diffusion; D004343:Drug Implants / Q000737:chemistry*; D008790:Metoprolol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008956:Models, Chemical; D009995:Osmosis; D016062:Porosity
chemical_list: D000319:Adrenergic beta-Antagonists; D004343:Drug Implants; C013517:ethyl cellulose; D002482:Cellulose; C008079:hydroxypropylcellulose; D008790:Metoprolol