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Few studies have investigated the internal processes involved in bioadhesive bond formation, particularly where mucus and hydrated polymer contribute jointly to bond structure. This paper reports the first study to spatially map the internal environment within a developing bioadhesive bond, utilising nuclear magnetic resonance (NMR) microscopy to measure localised water self-diffusion coefficients (SDC) and confocal laser scanning microscopy (CLSM) to estimate mucin concentration. In a model bioadhesive bond formed between an alginate matrix and mucin gel, characteristic profiles were observed in which fluorescence measurements showed a region of increasing mucin concentration in the mucus layer region adjacent to the matrix, corresponding closely with a zone of restricted water SDC in the diffusion profiles. These regions extended 144 μm (a normal human gastric layer thickness [Clin. Sci. 95 (1998) 97]) into the mucin layer after just 30 s, increasing to 800 μm after 30 min. The formation of a hydrated polymer layer at the matrix surface, confirmed visually, was also reflected in corresponding gradient changes. The results suggest a progressive dehydration of the mucus gel during bond formation, and the study demonstrates how together, these microscopies can provide non-invasive, quantitative, spatial and time-resolved evidence of internal hydration behaviour during bioadhesive bond formation. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]