Synchrotron X-ray microtomographic study of tablet swelling.
Tablet swelling behaviour was investigated by following the movements of embedded glass microsphere tracers, using X-ray microtomography (XmicroT) with intense illumination from a synchrotron. Specimens were prepared using combinations of hydroxypropyl-methyl-cellulose (HPMC) and microcrystalline cellulose (MCC) or pre-gelatinised starch (PGS), three materials commonly used as excipients for compacted tablets. The results revealed significant differences in swelling behaviour due to excipient type and compaction conditions. In particular, a sudden change was observed from gel-forming behaviour of formulations containing PGS or high HPMC content, to more rapid expansion and disintegration for formulations above 70% MCC. Although some radial expansion was observable with the higher PGS formulations and during later stages of swelling, axial expansion (i.e. the reverse of the compaction process) appeared to dominate in most cases. This was most pronounced for the 10/90 HPMC/MCC specimens, which rapidly increased in thickness, while the diameter remained almost unchanged. The expansion appeared to be initiated by hydration and may be due to the relaxation of residual compaction stress. This occurred within 'expansion zones', which initially appeared as thin bands close to the compacted (upper and lower) faces, but gradually advanced towards the centre and spread around the sides of the tablets. These zones exhibited lower X-ray absorbance, probably because they contained significant amounts of bubbles, which were formed by air released from the swelling excipients. Although, in most cases, these bubbles were too small to be resolved (<60 microm), larger bubbles (diameter up to 1mm) were clearly evident in the rapidly swelling 10/90 HPMC/MCC specimens. It is suggested that the presence of these bubbles may affect subsequent water ingress, by increasing the tortuosity and occluding part of the gel, which may affect the apparent diffusion kinetics (i.e. Fickian or Case II). These observations also suggested that axial expansion, initiated by water ingress, may be an important mechanism during tablet swelling.
Laity
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PR
Department of Materials Science and Metallurgy, University of Cambridge, Cambridge, UK. prl28@cam.ac.uk
Cameron
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D002482:Cellulose / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D005898:Glass; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008863:Microspheres; D013213:Starch / Q000737:chemistry; D017356:Synchrotrons; D013607:Tablets; D055114:X-Ray Microtomography / Q000379:methods*
D005079:Excipients; D005782:Gels; D013607:Tablets; D065347:Hypromellose Derivatives; D002482:Cellulose; D008747:Methylcellulose; D013213:Starch; C109691:microcrystalline cellulose