Application of a Compact Magnetic Resonance Imaging System with 1.5 T Permanent Magnets to Visualize Release from and the Disintegration of Capsule Formulations <i>in Vitro</i> and <i>in Vivo</i>

Abstract

Although magnetic resonance imaging (MRI) has potential in assessments of formulations, few studies have been conducted because of the size and expense of the instrument. In the present study, the processes of in vitro and in vivo release in a gelatin capsule formulation model were visualized using a compact MRI system with 1.5 T permanent magnets, which is more convenient than the superconducting MRI systems typically used for clinical and experimental purposes. A Gd-chelate of diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid, a contrast agent that markedly enhances proton signals via close contact with water, was incorporated into capsule formulations as a marker compound. In vitro experiments could clearly demonstrate the preparation-dependent differences in the release/disintegration of the formulations. In some preparations, the penetration of water into the formulation and generation of bubbles in the capsule were also observed prior to the disintegration of the formulation. When capsule formulations were orally administered to rats, the release of the marker into the stomach and its transit to the duodenum were visualized. These results strongly indicate that the compact MRI system is a powerful tool for pharmaceutical studies.Key words magnetic resonance imaging (MRI); capsule formulation; release; disintegration; gadoliniumchelate of diethylenetriamine-N,N,N′,N″,N″-pentaacetic acid (Gd-DTPA) Capsule formulations are convenient drug delivery systems that control the stability and release of drugs in the gastrointestinal tract; therefore, they are used in a wide range of drugs that are administered orally. The performance of formulations is influenced by the swelling and/or disintegration of capsules, the penetration of water in formulations, and the release of drug contents in the gastrointestinal tract. Since these processes influence the bioavailability of drugs, visualizing these processes may provide direct information for assessing capsule formulations.Magnetic resonance imaging (MRI) is a non-invasive imaging technique that provides unique information that is useful for diagnostic purposes. MRI is sensitive to the local concentrations and physical state of protons, mainly those in water in biological specimens. The advantages of MRI over other non-invasive imaging techniques such as γ-scintigraphy are its high spatial and temporal resolutions and representation of anatomical structures. Paramagnetic compounds such as chelate compounds of Gd(III) are typically used as contrast agents.1) Gd-chelates shorten the longitudinal relaxation time (T 1 ) of protons in water by making close contact with water, which markedly enhances proton signals on T 1 -weighted magnetic resonance (MR) images. In contrast, the dry form of Gd-chelates provides no signal on MR images without contact with water.2,3) The release of substances from tablets and capsules has been visualized in rats 3,4) and humans 2) using this technique. Despite its usefulness, few studies have employed MRI in pharmaceutical analyses because of ...