title: Mechanistic model for drug release during the lag phase from pellets coated with a semi-permeable membrane.
abstract: A new mechanistic model of drug release during the lag phase from coated pellets undergoing cracking in the coating due to the hydrostatic pressure built up inside the pellet has been developed. The model describes dynamically all the main release processes occurring during the lag phase in pellets coated with a semi-permeable membrane, i.e. the influx of solvent driven by the difference in osmotic pressure across the coating, dissolution of the drug, swelling of the pellet due to solvent accumulation, build-up of hydrostatic pressure inside the pellet, tensile stress acting on the coating, and the efflux of the dissolved drug. The water uptake is described using irreversible thermodynamics theory, while the tensile stress is described using solid mechanics theory. Importantly, the model allows the prediction of the lag time prior to crack formation. The effect of the pellet size, the pellet shape and the coating thickness on the lag time and on the lag phase release profile has been investigated via computer simulations. The model was validated by comparison with dose release data obtained from pellets coated with an ethyl-cellulose-based film. The good agreement found between the predicted release and the experimental data confirmed the validity of the model.
authors.affiliation: Department of Chemical Engineering, Lund University, P.O. Box 124, SE-221 00 Lund, Sweden.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Marucci
authors.forename: Gert
authors.initials: G
authors.lastname: Ragnarsson
authors.forename: Ulf
authors.initials: U
authors.lastname: Nyman
authors.forename: Anders
authors.initials: A
authors.lastname: Axelsson
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004343:Drug Implants; D008567:Membranes, Artificial; D008962:Models, Theoretical; D009997:Osmotic Pressure; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D017330:Remoxipride / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D013718:Tensile Strength
chemical_list: D004337:Drug Carriers; D004343:Drug Implants; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D017330:Remoxipride