title: Ethylcellulose film coating of guaifenesin-loaded pellets: A comprehensive evaluation of the manufacturing process to prevent drug migration.
abstract: The aim of the research was to investigate the complete process of pellet production in a Wurster fluidized bed coater in order to determine the main factors affecting the migration phenomenon of a soluble API through the ethycellulose film coating (Surelease®) and hence the long-term stability of the controlled release pellets. Guaifenesin (GFN), as BCS class I model drug, was layered on sugar spheres using a binder-polymer solution containing the dissolved GFN. The drug loaded pellets were then coated with Surelease®. The influence of drug loading (4.5-20.0% w/w), curing conditions (40-60°C and dynamic-static equipment), coating level (12-20% theoretical weight gain) and composition of the binder-layering solution (hypromellose versus Na alginate) on process efficiency (RSDW%), GFN content uniformity (RSDC%), GFN solid state (DSC and XRD) and pellet release profiles was evaluated. The effectiveness of the Surelease film was strongly affected by the ability of GFN to cross the coating layer and to recrystallize on the pellet surface. Results indicated that this behaviour was dependent on the polymer used in the binder-layering solution. Using hypromellose as polymer, GFN recrystallized on the coated pellet surface at both drug loadings. The curing step was necessary to stabilize the film effectiveness at the higher drug loading. Increasing the coating level delayed but did not prevent the GFN diffusion. Replacing hypromellose with Na alginate, reduced the migration of GFN through the film to a negligible amount even after six months of storage and the curing step was not necessary to achieve stable controlled release profiles over storage.
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Melegari
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Bertoni
authors.affiliation: Colorcon Ltd, Victory Way, Dartford ME10 5JJ, UK.
authors.forename: Alberto
authors.initials: A
authors.lastname: Genovesi
authors.affiliation: Colorcon Ltd, Victory Way, Dartford ME10 5JJ, UK.
authors.forename: Kevin
authors.initials: K
authors.lastname: Hughes
authors.affiliation: Colorcon, Inc., 275 Ruth Road, Harleysville, PA 19438, USA.
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rajabi-Siahboomi
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Passerini
authors.affiliation: Department of Pharmacy and BioTechnology, University of Bologna, Via S. Donato 19/2, 40127 Bologna, Italy. Electronic address: beatrice.albertini@unibo.it.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Albertini
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004343:Drug Implants / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D065546:Drug Liberation; D006140:Guaifenesin / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014961:X-Ray Diffraction
chemical_list: D004343:Drug Implants; D006140:Guaifenesin; C013517:ethyl cellulose; D002482:Cellulose
keywords: Curing; Drug layering; Ethylcellulose; Film coating; Guaifenesin; Hypromellose; Sodium alginate; Stability; Surelease