title: Release of poorly soluble drugs from HPMC tablets studied by FTIR imaging and flow-through dissolution tests.
abstract: Spectroscopic imaging and a flow-through dissolution test have been combined to improve the possibilities of investigating the release of a poorly soluble drug (diclofenac) from pharmaceutical tablets. The presented methods aim to overcome the limitations that impede the conventional dissolution test because of its inability to observe precipitates of poorly soluble drug during tablet dissolution. The proposed flow-through set-up allows small drug particles that are being carried along in the water-flow to be analyzed, by adding a dissolution agent to the medium after it left the tablet cell. Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopic imaging provides an insight into the processes inside the tablet and is not hindered by insoluble or recrystallising drug. The techniques have been hyphenated and used to study tablets containing diclofenac sodium and HPMC (hydroxypropyl methylcellulose) in different dissolution media that influence the solubility of the drug. The release profiles obtained by flow-through dissolution test suggest the presence of particles (or precipitates) in the dissolution medium. This is consistent with the results obtained by FTIR imaging, which confirms that both proposed techniques are superior to the ordinary dissolution test when applied to poorly soluble drugs. FTIR imaging data have been analyzed by a classical least squares analysis, corrected for the parts of the tablet outside the field of view, and used to calculate the release profile. The infrared spectra of diclofenac at varying relative humidity were acquired to study the interactions of diclofenac and water, including identification of dissociated diclofenac, thus the chemical specificity of FTIR imaging was fully utilized.
authors.affiliation: Department of Chemical Engineering and Chemical Technology, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Jaap
authors.initials: J
authors.lastname: van der Weerd
authors.forename: Sergei G
authors.initials: SG
authors.lastname: Kazarian
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004008:Diclofenac / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D065347:Hypromellose Derivatives; D016018:Least-Squares Analysis; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D013607:Tablets / Q000737:chemistry*; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D013607:Tablets; D014867:Water; D004008:Diclofenac; D065347:Hypromellose Derivatives; D008747:Methylcellulose