Ragnar Ek

Compression behaviour and compactability of microcrystalline cellulose pellets in relationship to their pore structure and mechanical properties

Abstract Two series of microcrystalline cellulose pellets were produced by extrusion-spheronization and the size fraction 710–1000 μm was prepared by sieving. The preparation procedure gave nearly spherical pellets with similar shape and surface characteristics but markedly different porosity and mechanical properties. The pellets compressed by permanent deformation rather than by fragmentation. The degree of pellet deformation increased with an increased original pellet porosity while the mechanical strength of the pellets was not a primary factor in the compression behaviour of the pellets. The compactability of the pellets related directly to the original pellet porosity. The results indicate thus that the pellet porosity determined the degree of their deformation during compression which in turn controlled the pore structure and the tensile strength of the compact formed. A high degree of pellet deformation gave a low intergranular separation distance in the compact and promoted the formation of intergranular bonds of a high bonding force.

Crystallinity index of microcrystalline cellulose particles compressed into tablets

The crystallinity index of compressed microcrystalline cellulose particles has been estimated using 13C CP/MAS NMR and photoacoustic FTIR. The results indicate a slight initial increase in crystallinity followed by a decrease as the compaction pressure increases. The initial increase is explained as a transformation of strained structures in cellulose particles into more ordered forms as a result of the initial compression. At higher compaction pressures the crystallinity begins to decrease. This change in crystallinity seems to be larger on the tablet surface than in the tablet bulk and even larger at the tablet perimeter surface than on the top or bottom surfaces of the tablet. Our explanation for these findings is that these differences reflect different levels of shearing forces acting on different parts of the tablet during compaction.

What to do with all these algae

Abstract The severe eutrophication of coastal areas is considered to be one of the most serious environmental threats of our time S. Nixon, Ambio 19 (1990) 101. Even if the nutrient outlet is curtailed, carpets of green algae filaments will remain for a long time as the algae life cycle feeds itself S. Naeem, D.R. Hahn, G. Schuurman, Nature 403 (2002) 762. One way to master this ecological problem is to remove algae from the cycle O. Jousson, J. Pawlowski, L. Zaninetti, F.W. Zechman, F. Dini, G. Di Guiseppe, R. Woodfield, A. Millar, A. Meinensz, Nature 408 (2000) 157. Hence, the necessity of finding some relevant use for green algae is obvious. It has been shown that cellulose powder from green algae sources has a higher level of crystallinity and a relatively larger surface area than higher plant cellulose R. Ek, C. Gustafsson, A. Nutt, T. Iversen, C, Nystrom, J. Mol. Recognit. 11 (1998) 263. Could these properties possibly be advantageous in pharmaceutical tablet manufacturing? Here, we show that green algae filaments provide an alternative raw material source for the production of microcrystalline cellulose with a hitherto unobserved combination of properties desirable for a tableting excipient.

Microcrystalline Cellulose as a Sponge as an Alternative Concept to the Crystallite-Gel Model for Extrusion and Spheronization

Microcrystalline cellulose as a sponge as an alternative concept to the crystallite-gel model for extrusion and spheronization

Particle analysis of microcrystalline cellulose : differentiation between individual particles and their agglomerates

Abstract The presence of two types of particles, the individual particles and their agglomerates, complicates the characterization of the particle size and the external surface area in the microcrystalline cellulose powders. During characterization, different degrees of de-agglomerations may be applied with varying size and surface areas as a result. The crystallinity of the cellulose particles were characterized by a crystallinity index, using the solid state NMR technique. Methods for the characterization of particle size, surface, shape of individual particles and their agglomerates were examined and recommendations of suitable methods are given. Individual particles were separated from agglomerates by ultrasonic treatment of a water suspension of agglomerates. Photoextinction measurements on sonicated water suspensions were used in the characterization of size and surface area of individual particles. The size of the agglomerates were estimated by dry sieving and the external surface area of the agglomerates with photoextinction measurements on cyclohexane suspensions not treated with ultrasonic energy.

Pore swelling in beads made of cellulose fibres and fibre fragments

Abstract The swelling of a new pharmaceutical excipient consisting of highly porous cellulose beads has been studied. Different degrees of swelling were produced by absorption of water and cyclohexane, two liquids with different ‘swelling capacity’. The pore size in cellulose beads with different porosities was investigated using the spin echo NMR technique and found to increase due to swelling. The crystallinity of dry and wet cellulose fibres was investigated using 13 C CP/MAS NMR. A basic application of the beads is to use them as well-defined drug carrier particles. The beads can be loaded with drugs by a sorption process from water or organic solvents. It was concluded that it is beneficial to load the beads using drug solutions containing a cellulose swelling liquid.

Prediction of drug release by characterisation of the tortuosity in porous cellulose beads using a spin echo NMR technique

Abstract The tortuosity of pores in cellulose beads has been estimated using a spin echo NMR technique and by direct release measurements. The tortuosity determined with NMR was slightly higher ( r = 2.7) than the values obtained from direct release measurements ( r = 1.6-2.4). The deviations are explained in terms of unfulfilled prerequisites for the models describing the dissolution process. Another explanation may be differences in drug loading and pore structure in the outer and inner layer of the porous cellulose beads. The NMR measurements are described in detail and special problems occurring when applying this technique are discussed. In this work it is shown to be possible to predict drug release from structural data of porous cellulose beads.

Characterisation of instantaneous water absorption properties of pharmaceutical excipients.

Powders absorb water by both capillary imbibition and swelling. The capillary process is almost instantaneous but swelling occurs over a period of time. An isothermal transient ionic current technique was used in this study to characterise the instantaneous absorption properties (rate and capacity) of a few selected pharmaceutical excipients. The results indicate that the instantaneous and long term water absorption properties of pharmaceutical powders can differ considerably. The rate of instantaneous water absorption appears to correlate with the total surface area while the absorption capacity correlates more with the porosity of the powder.

Densification-induced conductivity percolation in high-porosity pharmaceutical microcrystalline cellulose compacts

The percolation theory is established as a useful tool in the field of pharmaceutical materials science. It is shown that percolation theory, developed for analyzing insulator–conductor transitions, can be applied to describe imperfect dc conduction in pharmaceutical microcrystalline cellulose during densification. The system, in fact, exactly reproduces the values of the percolation threshold and exponent estimated for a three-dimensional random continuum. Our data clearly show a crossover from a power-law percolation theory region to a linear effective medium theory region at a cellulose porosity of ∼0.7.

A new method of characterising liquid uptake within particles over short time periods.

A method of measuring both the capacity and rate of absorption of liquid by powders of small particles over short time periods (of the order of a few seconds or less) is presented. The method is based on the measurement of the isothermal transient ionic current in a sample cell containing the absorbant material and the liquid. The method has been tested on solid glass beads, porous glass beads and cellulose agglomerates. Properties such as the instantaneous absorption capacity and rate can be characterised within a few seconds. No other technique is currently able to measure these fast outcomes.