Research paper Assessing gastrointestinal motility and disintegration profiles of magnetic tablets by a novel magnetic imaging device and gamma scintigraphy Kirsteen Goodman a, * , Lee Ann Hodges b , Janet Band b , Howard N.E. Stevens a,b , Werner Weitschies c , Clive G. Wilson a,b a Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK b Bio-Images Research Ltd., Glasgow, UK c Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Greifswald, Germany article info Article history: Received 4 July 2008 Accepted in revised form 13 January 2009 Available online 20 January 2009 Keywords: Gastrointestinal motility Magnetic tablets Magnetic imaging Gamma scintigraphy abstract Purpose: To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and disintegration of solid dosage forms and to correlate the MMI findings with the corresponding gamma scintigraphic data. Materials and methods: Three magnetic tablets (MTs) were investigated using in vitro and in vivo tests. The clinical study was a four-way, crossover study with the following arms: (a) immediate-release tablets administered in fasted state; (b) immediate-release tablets administered after 400 mL of Clinutren Ò ISO; (c) enteric-coated tablets administered in the fasted state; and (d) non-disintegrating tablets studied in the lightly fed state (100 mL of Clinutren Ò ISO). Results: In both the in vitro and in vivo studies, tablets were detected successfully by MMI and scintigra- phy. There was a good correlation between gastric residence times and positional data (in the x, y and y, z-axes). In addition, MMI revealed early swelling behaviour of the tablet matrix. There was excellent agreement for the disintegration times of MT(A) in the fasted arm (scintigraphy 12.0 ± 4.4 min, MMI 11.8 ± 4.4 min). In the MT(A)-fed arm, onset times determined by scintigraphy were delayed in three sub- jects when compared to the corresponding MMI results. Delayed disintegration was observed with MT(A) administered after food (p < 0.01) in both the techniques. Conclusion: The MMI device is a reliable imaging tool for tracking the transit and disintegration of a mag- netic tablet through the gastrointestinal tract. Ó 2009 Elsevier B.V. All rights reserved. 1. Introduction The use of the gamma camera to study novel formulations in man was reported in the late 70s [1,2] and since then it has remained the ‘gold standard’ imaging technique to study the in vivo characteristics of orally administered formulations such as tablets, capsules and multi-particulates [3–10]. Although highly utilised, the drawbacks of gamma scintigraphy include the radia- tion exposure to the volunteer, which minimises the number of repeat studies and restricts its use in women and children. In some countries, the use of radiation is prohibited in healthy individuals, and the instrumentation is neither portable nor widely available. Alternative imaging techniques such as ultrasound and 13 C-octanoic breath tests have been validated against gamma scin- tigraphy for the investigation of motility and transit parameters [11,12]. These methods are used for diagnosis, but are really not adaptable for the study of dosage forms as required by the pharma- ceutical scientists. A bio-magnetic method known as Magnetic Moment Imaging (MMI) is a novel technique which is of increasing interest in clini- cal, physiological and pharmaceutical researches. An appropriate magnetic measuring device is used to measure the magnetic field generated from a magnetically tagged solid dosage form whilst in the gastrointestinal tract. The magnetic field generated by the magnetic dipole moment penetrates the tissue without distortions which can then be detected non-invasively from outside the body. Ferrous materials such as iron oxide (Fe 3 O 4 , food colourant E172) and manganese ferrite (MnFe 2 O 4 ) have been used to magnetically label dosage forms and meals [23–26], and permanent magnets have also been utilised to study the physiological aspects of gastro- intestinal motility [27–31]. Superconducting Quantum Interference Devices (SQUIDS) are the most highly sensitive magnetic sensors used for MMI. This technique has been used to study the behaviour of disintegrating capsules [13] and non-disintegrating capsules [14,15], and the 0939-6411/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ejpb.2009.01.004 * Corresponding author. Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0NR, UK. Tel.: +44 07980975410; fax: +44 01312429447. E-mail address: Kristeen.goodman@ed.ac.uk (K. Goodman). European Journal of Pharmaceutics and Biopharmaceutics 74 (2010) 84–92 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb