title: Dissolution of tablet-in-tablet formulations studied with ATR-FTIR spectroscopic imaging.
abstract: This work uses ATR-FTIR spectroscopic imaging to study the dissolution of delayed release and pH resistant compressed coating pharmaceutical tablets. Tablets with an inner core and outer shell were constructed using a custom designed compaction cell. The core of the delayed release tablets consisted of hydroxypropyl methylcellulose (HPMC) and caffeine. The shell consisted of microcrystalline cellulose (MCC) and glucose. The core of the pH resistant formulations was an ibuprofen and PEG melt and the shell was constructed from HPMC and a basic buffer. UV/vis spectroscopy was used to monitor the lag-time of drug release and visible optical video imaging was used as a complementary imaging technique with a larger field of view. Two delayed release mechanisms were established. For tablets with soluble shell sections, lag-time was dependent upon rapid shell dissolution. For tablets with less soluble shells, the lag-time was controlled by the rate of dissolution medium ingress through the shell and the subsequent expansion of the wet HPMC core. The pH resistant formulations prevented crystallization of the ibuprofen in the core during dissolution despite an acidic dissolution medium. FTIR imaging produced important information about the physical and chemical processes occurring at the interface between tablet sections during dissolution.
authors.affiliation: Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Wray
authors.forename: Graham S
authors.initials: GS
authors.lastname: Clarke
authors.forename: Sergei G
authors.initials: SG
authors.lastname: Kazarian
mesh_terms: D002110:Caffeine / Q000737:chemistry; D002482:Cellulose / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D007052:Ibuprofen / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013607:Tablets / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D002110:Caffeine; D065347:Hypromellose Derivatives; D011092:Polyethylene Glycols; D002482:Cellulose; D008747:Methylcellulose; D005947:Glucose; C109691:microcrystalline cellulose; D007052:Ibuprofen