title: Combined study of biphasic and zero-order release formulations with dissolution tests and ATR-FTIR spectroscopic imaging.
abstract: In this study of multi-layer tablets, the dissolution of biphasic and zero-order release formulations has been studied primarily using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic imaging as well as UV-Vis detection of dissolved drug in the effluent stream and USP dissolution testing. Bilayer tablets, containing the excipients microcrystalline cellulose (MCC) and glucose, were used for biphasic release with nicotinamide and buflomedil as model drugs. ATR-FTIR spectroscopic imaging showed the changing component distributions during dissolution. Further experiments studied monolithic and barrier-layered tablets containing hydroxypropyl methylcellulose, MCC and buflomedil dissolving in a USP I apparatus. These data were compared with UV-Vis dissolution profiles obtained online with the ATR flow-through cell. ATR-FTIR imaging data of the biphasic formulations demonstrated that the drug release was affected by excipient ratios and effects such as interference between tablet sections. Tablets placed in the ATR-FTIR flow-through cell exhibited zero-order UV-Vis dissolution profile data at high flow rates, similar to barrier-layered formulations studied using the USP I apparatus. ATR-FTIR spectroscopic imaging provided information regarding the dissolution mechanisms in multi-layer tablets which could assist formulation development. The ability to relate data from USP dissolution tests with that from the ATR-FTIR flow-through cell could help spectroscopic imaging complement dissolution methods used in the industry.
authors.affiliation: Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: Wray
authors.affiliation: Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Ling Qiao
authors.initials: LQ
authors.lastname: Li
authors.affiliation: Department of Chemical Engineering, Imperial College London, London SW7 2AZ, United Kingdom. Electronic address: s.kazarian@imperial.ac.uk.
authors.forename: Sergei G
authors.initials: SG
authors.lastname: Kazarian
mesh_terms: D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005947:Glucose / Q000737:chemistry; D009536:Niacinamide / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets
chemical_list: D004338:Drug Combinations; D005079:Excipients; D011759:Pyrrolidines; D013607:Tablets; D009536:Niacinamide; D002482:Cellulose; D005947:Glucose; C109691:microcrystalline cellulose; C010651:buflomedil
keywords: ATR-FTIR spectroscopy; FTIR spectroscopic imaging; biphasic delivery; controlled release; dissolution; drug release; imaging methods; spectroscopic imaging; tableting; zero-order release