title: Effects of film coating thickness and drug layer uniformity on in vitro drug release from sustained-release coated pellets: a case study using terahertz pulsed imaging.
abstract: Film coating thickness and terahertz electric field peak strength (TEFPS) were determined using terahertz pulsed imaging (TPI) and employed for the analysis of sustained-release coated pellets (theophylline layered sugar cores coated with Kollicoat SR:Kollicoat IR polymer blends). The effects of coating thickness, drug layer uniformity and optional curing were investigated using eight batches of pellets. Ten pellets from each batch were imaged with TPI to analyse the coating morphology (depicted in TEFPS) and thickness prior to release measurements. The results showed TEFPS values of 15.8% and 14.5% for pellets with a smooth drug layer coated at 8.2 and 12.5% (w/w) polymer weight-gain, respectively. Whereas 6.7% was derived for pellets with a coarse drug layer coated at both weight-gains. Although there were major differences in TEFPS, the resulting drug release kinetics were very similar. It was also shown that a 36 microm coating thickness difference was not drug release rate determining. These results suggested that drug release for the pellets studied was not predominately governed by drug diffusion through the polymeric film coating but probably to a large extent limited by drug solubility. TPI proved to be highly suitable to detect non-homogeneities in the drug layer and polymeric film coating.
authors.affiliation: School of Pharmacy, University of Otago, P.O. Box 56, Dunedin, New Zealand. louise.ho@otago.ac.nz
authors.forename: Louise
authors.initials: L
authors.lastname: Ho
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Cuppok
authors.forename: Susanne
authors.initials: S
authors.lastname: Muschert
authors.forename: Keith C
authors.initials: KC
authors.lastname: Gordon
authors.forename: Michael
authors.initials: M
authors.lastname: Pepper
authors.forename: Yaochun
authors.initials: Y
authors.lastname: Shen
authors.forename: Florence
authors.initials: F
authors.lastname: Siepmann
authors.forename: Juergen
authors.initials: J
authors.lastname: Siepmann
authors.forename: Philip F
authors.initials: PF
authors.lastname: Taday
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004058:Diffusion; D004339:Drug Compounding; D007700:Kinetics; D008956:Models, Chemical; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*; D055069:Terahertz Imaging; D013806:Theophylline / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; C519734:Kollicoat IR; D011145:Polyvinyls; D013607:Tablets; C013215:polyvinyl acetate; D013806:Theophylline