Synchrotron X-ray microtomographic study of tablet swelling. 2010

P R Laity, and R E Cameron
Department of Materials Science and Metallurgy, University of Cambridge, Cambridge, UK. prl28@cam.ac.uk

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.

UI MeSH Term Description Entries
D008747 Methylcellulose Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. BFL,Celevac,Cellothyl,Cellulone,Citrucel,Cologel,Dacryolarmes,Methocel,Methyl Cellulose,Muciplasma,Cellulose, Methyl
D008863 Microspheres Small uniformly-sized spherical particles, of micrometer dimensions, frequently labeled with radioisotopes or various reagents acting as tags or markers. Latex Beads,Latex Particles,Latex Spheres,Microbeads,Bead, Latex,Beads, Latex,Latex Bead,Latex Particle,Latex Sphere,Microbead,Microsphere,Particle, Latex,Particles, Latex,Sphere, Latex,Spheres, Latex
D002482 Cellulose A polysaccharide with glucose units linked as in CELLOBIOSE. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. Alphacel,Avicel,Heweten,Polyanhydroglucuronic Acid,Rayophane,Sulfite Cellulose,alpha-Cellulose,Acid, Polyanhydroglucuronic,alpha Cellulose
D002626 Chemistry, Pharmaceutical Chemistry dealing with the composition and preparation of agents having PHARMACOLOGIC ACTIONS or diagnostic use. Medicinal Chemistry,Chemistry, Pharmaceutic,Pharmaceutic Chemistry,Pharmaceutical Chemistry,Chemistry, Medicinal
D005079 Excipients Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form. These include binders, matrix, base or diluent in pills, tablets, creams, salves, etc. Excipient,Stabilizing Agent,Stabilizing Agents,Suspending Agent,Suspending Agents,Agent, Stabilizing,Agent, Suspending,Agents, Stabilizing,Agents, Suspending
D005782 Gels Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
D005898 Glass Hard, amorphous, brittle, inorganic, usually transparent, polymerous silicate of basic oxides, usually potassium or sodium. It is used in the form of hard sheets, vessels, tubing, fibers, ceramics, beads, etc.
D013213 Starch Any of a group of polysaccharides of the general formula (C6-H10-O5)n, composed of a long-chain polymer of glucose in the form of amylose and amylopectin. It is the chief storage form of energy reserve (carbohydrates) in plants. Amylomaize Starch,Amylum,Cornstarch,Keoflo,Starch, Amylomaize
D013607 Tablets Solid dosage forms, of varying weight, size, and shape, which may be molded or compressed, and which contain a medicinal substance in pure or diluted form. (Dorland, 28th ed) Tablet
D017356 Synchrotrons Devices for accelerating protons or electrons in closed orbits where the accelerating voltage and magnetic field strength varies (the accelerating voltage is held constant for electrons) in order to keep the orbit radius constant. Synchrotron

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