title: Polymer leaching from film coating: effects on the coating transport properties.
abstract: The release mechanism of metoprolol succinate pellets coated with a blend of a water-insoluble polymer, ethyl cellulose (EC), and a water-soluble polymer, hydroxypropyl cellulose (HPC), is mechanistically explained. The kinetics of drug release and HPC leaching were followed for drug doses. The coating was initially not permeable to the drug, and release started only after a critical amount of the HPC had been leached out. Drug release occurred mainly through pores created in the coating by the HPC dissolution. Single-pellet release experiments were also performed. The coating thickness and size of each pellet were measured. In order to quantitatively characterize the transport properties of the coating of the individual pellets, and to determine the effective diffusion coefficient (D(e)) of the drug in the coating, a mechanistic model was used to fit the single-pellet release data. It was found that D(e) increased with time due to an increase in the amount of HPC leached. It was also found that D(e) was dependent on the coating thickness, and increased more slowly with a thicker coating. This agreed well with the finding that the HPC leaching rate decreased with increasing film thickness.
authors.affiliation: Department of Chemical Engineering, Lund University, PO 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: Christian
authors.initials: C
authors.lastname: von Corswant
authors.forename: Anette
authors.initials: A
authors.lastname: Welinder
authors.forename: Annica
authors.initials: A
authors.lastname: Jarke
authors.forename: Frida
authors.initials: F
authors.lastname: Iselau
authors.forename: Anders
authors.initials: A
authors.lastname: Axelsson
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D001692:Biological Transport; D002482:Cellulose / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D008422:Materials Testing; D008790:Metoprolol / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics; D008956:Models, Chemical; D011108:Polymers; D012995:Solubility; D013607:Tablets / Q000737:chemistry
chemical_list: D000319:Adrenergic beta-Antagonists; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013607:Tablets; C013517:ethyl cellulose; D002482:Cellulose; C008079:hydroxypropylcellulose; D008790:Metoprolol