Application of a Biomagnetic Measurement System (BMS) to the Evaluation of Gastrointestinal Transit of Intestinal Pressure-Controlled Colon Delivery Capsules (PCDCs) in Human Subjects
Purpose. For determination of the transit time through various partsof the gastrointestinal (GI) tract, we developed a method that providesthe location of disintegration and drug release. This method involves GImagnetomarkergraphy (GIMG) using a 129-channel Shimadzu vectorbiomagnetic measurement system (BMS).
Methods. To magnetically label the pressure-controlled colon deliverycapsule (PCDC) containing 75.0 ± 0.5 mg of caffeine as a tracer drug,small capsule caps containing 90 mg of ferric oxide powdered magnetite(Fe2O3) were attached to PCDCs. After orally administration to fastedhuman volunteers, saliva samples were collected hourly and salivarycaffeine concentration was measured. At the same time, locations ofthe magnetic PCDC were detected by BMS just after the PCDCs weremagnetized with the coils of a magnetic resonance imaging (MRI)system. The magnetic field distributions were analyzed and theestimated positions were shown on the MRI picture of the same subject'sabdominal structure.
Results. We magnetized PCDC with permanent magnets or anelectromagnet before ingestion and the estimated locations of PCDC in the GItract exhibited high estimation error. In order to increase the precision ofestimated localization of PCDCs, PCDCs were magnetized within thecoils of the MRI. As a result, these PCDCs had strong magnetic dipolesthat were parallel to the sensor unit of BMS in every measurement,and therefore the spatial resolution of the PCDC's two-dimensionalpositions in the organs of the GI tract was within a range of severalmillimeters.
Conclusions. GIMG is a powerful tool for the study of colon deliveryefficiencies of PCDCs. The main advantage of GIMG is the capabilityto obtain even more detailed knowledge of the behavior and fate ofsolid pharmaceutical formulations during GI passage.
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- 1.A. B. Hawthorne and C. J. Hawkey. Immunosuppressive drugs in inflammatory bowel disease. A review of their mechanisms of efficacy and place in therapy. Drugs. 38:267-288 (1989).Google Scholar
- 2.H. B. Stephen. Inflammatory bowel disease. Drug Ther. 334:841-848 (1996).Google Scholar
- 3.S. S. Davis. Delivery systems for biopharmaceuticals. J. Pharm. Pharmacol. 44:186-190 (1992).Google Scholar
- 4.M. E. K. Kraeling and W. A. Ritschel. Development of colonic release capsule iosage form and the absorption of insulin. Meth. Find. Exp. Clin. Pharmacol. 14:199-209 (1992).Google Scholar
- 5.D. T. O'Hagan, K. J. Palin, and S. S. Davis. Intestinal absorption of proteins and macromolecules and the immunological response. CRC Crit. Rev. Ther. Drug Carrier Sys. 4:197-220 (1987).Google Scholar
- 6.V. H. L. Lee. Enzymatic barriers to peptide and protein absorption. CRC Crit. Rev. Ther. Drug Carrier Sys. 5:69-97 (1988).Google Scholar
- 7.J. F. Woodley. Enzymatic barriers for FI peptide and protein delivery. Crit. Rev. Ther. Drug Carrier Sys. 11:61-95 (1994).Google Scholar
- 8.R. J. Mrsny. The colon as a site for drutg delivery. J. Contr. Rel. 22:15-34 (1992).Google Scholar
- 9.D. R. Friend. Oral colon-specific drug delivery. CRC Press, Inc., Florida. (1992).Google Scholar
- 10.M. Motoki, Z. Hu, T. Shimokawa, S. Sekino, K. Rie, Y. Kuoi, Y. Yoshikawa, and K. Takada. Evaluation of intestinal pressure-controlled colon delivery capsule containing caffeine as a model drug in human volunteers. J. Contr. Rel. 52:119-129 (1998).Google Scholar
- 11.T. Takaya, C. Ikeda, N. Imagawa, K. Niwa, and K. Takada. Development of colon delivery capsule and the pharmacological activity of recombinant human granulocyte colony-stimulating factor (rhG-CFS) in beagle dogs. J. Pharm. Pharmacol. 47:474-478 (1995).Google Scholar
- 12.A. Kiriyama, T. Nishiura, M. Ishino, Y. Yamamoto, I. Ogita, Y. Kiso, and K. Takada. Binding characteristics of KNI-272 to plasma proteins, a new potent tripeptide HIV protease inhibitor KNI 272 in enteric capsule, Biopharm. Drug Dispos. 17:739-751 (1996).Google Scholar
- 13.T. Takaya, K. Sawada, H. Suzuki, A. Funaoka, K. Matsuda, and K. Takada. Application of colon delivery capsule to 5-aminosalicylic acid and evaluation of the pharmacokinetic profile after oral administration to beagle dogs, J. Drug Target. 4:271-276 (1997).Google Scholar
- 14.Z. Hu, G. Kimura, S. Mawatari, T. Shimokawa, Y. Yoshikawa, and K. Takada. New preparation method of intestinal pressure-controlled colon delivery capsules by coating machine and evaluation in beagle dogs. J. Contr. Rel. 56:293-302 (1998).Google Scholar
- 15.G. A. Digenis, E. P. Sandefer, C. Richard, and D. Waoter. Gamma scintigraphy: an evolving technology in pharmacentical formulation development-part 1. Rev. Res. Focus. 1:100-108 (1998).Google Scholar
- 16.G. A. Digenis, E. P. Sandefer, C. Richard, and D. Waoter. Gamma scintigraphy: an evolving technology in pharmacentical formulation development-part 2. Rev. Res. Focus. 1:160-166 (1998).Google Scholar
- 17.T. Ishibashi, G.R. Pitcairn, H. Yoshino, M. Mizobe, and I. R. Wilding. Scintigraphic evaluation of a new capsule-type colon specific drug delivery system in healthy volunteers. J. Pharm. Sci. 87:531-535 (1998).Google Scholar
- 18.W. Werner, K. Roman, C. Dino, and T. Lutz. High-resolution monitoring of the gastrointestinal transit of a magnetically marked capsule. J. Pharm. Sci. 86:1218-1222 (1997).Google Scholar
- 19.J. Hughes and J Cohen. Relationship of the magnetoencephalogram to abnormal activity in the electroencephalogram. J. Neurol, 217:79-93 (1977).Google Scholar
- 20.G. M. Baule and R. McFee, Detection of the magnetic field of the heart. Am. Heart J. 66:95-96 (1963).Google Scholar
- 21.D. Cohen. Magnetoencephalography: Evidencee of magnetic fields produced by alpha-rhythms currents. Science. 161:784-786 (1968).Google Scholar
- 22.Y. Yoshida, A. Arakawa, A. Kondo, Y. Kajihara, S. Tomita, and Y. Takanashi. A 129 channel vector meuro-magnetic imaging System. Adv. Biomagnet. Abs. 351 (1996).Google Scholar
- 23.A. Melander. Influence of food on the bioavailability of drugs. Clin. Pharmacokin., 3:337-351 (1978).Google Scholar