title: Modulating pH-independent release from coated pellets: effect of coating composition on solubilization processes and drug release.
abstract: The aim of the study was to clarify the influences of three coating parameters on the drug release from chlorpheniramine maleate (CPM) pellets, coated with blends of poly(vinyl acetate) (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A central composite design was implemented to investigate the effect of the polymer blend ratio, the film coat thickness and the plasticizer concentration on the drug release. The solubilization inside the pellets was monitored by EPR spectroscopy. The blending ratio of both the polymers and the film thickness were found to have a major influence on the drug release and the solubilization speed, in contrast to the plasticizer concentration. A pH-independent release profile was adjustable via modulating the polymer blend ratio and the coating thickness. A mathematical model was developed, providing a good predictability of the release profile, based on the film coat composition. This model offers the possibility to achieve a defined drug-release profile by selective adaptation of the film coat composition, in view of process times, feasibility or polymer costs.
authors.affiliation: Technical Research & Development, Novartis Pharma AG, Basel, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Ensslin
authors.forename: Klaus Peter
authors.initials: KP
authors.lastname: Moll
authors.forename: Hendrik
authors.initials: H
authors.lastname: Metz
authors.forename: Markus
authors.initials: M
authors.lastname: Otz
authors.forename: Karsten
authors.initials: K
authors.lastname: Mäder
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000295:instrumentation* / Q000379:methods*; D002744:Chlorpheniramine / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000737:chemistry; D015195:Drug Design; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D008962:Models, Theoretical; D004364:Pharmaceutical Preparations; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D012995:Solubility; D013113:Spin Labels; D013678:Technology, Pharmaceutical / Q000295:instrumentation / Q000379:methods
chemical_list: D003497:Cyclic N-Oxides; D005079:Excipients; D004364:Pharmaceutical Preparations; D011108:Polymers; D011145:Polyvinyls; D013113:Spin Labels; C013215:polyvinyl acetate; D002744:Chlorpheniramine; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; C001803:tempol