Investigating the coating dependent release mechanism of a pulsatile capsule using NMR microscopy

J.C.D. Sutch, A. Ross, W. Köckenberger, R.W. Bowtell, J.R. MacRae, H. Stevens, C.D. Melia

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Chronopharmaceutical capsules, ethylcellulose-coated to prevent water ingress, exhibited clearly different release characteristics when coated by organic or aqueous processes. Organic-coated capsules produced a delayed pulse release, whereas aqueous-coated capsules exhibited less delayed and more erratic release behaviour. Nuclear magnetic resonance microscopy was used to elucidate the internal mechanisms underlying this behaviour by studying the routes of internal water transport and the timescale and sequence of events leading to the pulse. Images showed that the seal between the shell and the tablet plug is a key route of water penetration in these dosage forms. There is evidence for a more efficient seal in the organic-coated capsule, and although some hydration of the contents was evident, erosion of the tablet plug is most probably the controlling factor in timed release. The premature failure of the aqueous-coated capsule appears to be a result of rapid influx of water between plug and capsule with hydration of the low substituted hydroxypropylcellulose expulsion agent. As a result of this, the tablet plug remains intact, but appears unable to be ejected. The resulting significant pressure build-up causes premature release by distortion and splitting of the capsule shell. These events may be aided by a weakening of the aqueous-coated gelatin shell by hydration from the inside, and at the mouth of the capsule where previous electron microscope studies have shown incomplete coating of the inside by the aqueous process.
Original languageEnglish
Pages (from-to)341-347
Number of pages7
JournalJournal of Controlled Release
Issue number3
Publication statusPublished - 2003


  • pulsatile capsule
  • NMR microscopy
  • magnetic resonance imaging

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