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Cavities and the architectures inside tablet play a decisive role for the permeation of water within tablet to initiate disintegration phenomenon. The present study aims to establish inner structure characterization methodology based on synchrotron radiation X-ray microcomputed tomography (SR-μCT) for microcrystalline cellulose (MCC) tablets and to correlate the cavities and 'their attributes to tablet disintegration phenomenon. The three-dimensional (3D) morphological architecture and quantitative data of single particles for 12 specifications of MCC, and respective MCC tablets' cavities structure were obtained through advanced SR-μCT studies. The image processing techniques were established to study the morphology of voids and porosity in an axial and radial direction based on the highly resolved 3D structure of tablets. The in-situ visualization of morphological disintegration behavior indicates that there were two patterns of disintegrations, which can be cataloged as laminating type (LT) and splitting type (ST) disintegrations. The principal component analysis (PCA) was used for multivariate data analysis to get the meaningful correlation among disintegration behaviors, cavities morphology, single particles attributes, and the cavities spatial arrangement within the tablets. These findings have deepened insights into inner structures of tablets and single particle structural attributes to tablet disintegration, reflecting the mechanism of disintegration mode, and the significance of pharmaceutical structure evaluated via SR-μCT.

Sedimentation of non-homogeneous systems is the typical phenomenon indicating the physical instability as a key measure to the quality control of the preparation products. Currently, the determination methods for the sedimentation of non-homogeneous preparations are based on manual measurement or semi-quantitative observation, lacking of either automation or quantitative dynamic analysis. The purpose of this research was to realize automatic and quantitative monitoring of the sedimentation dynamics for non-homogenous systems as suspension, emulsions at laboratory level. Non-contact measurement method has been established to determine the sedimentation behaviors in a standard quartz tube for sedimentation, with internal diameter and height 23 mm and 215 mm, respectively, with controlled temperature and light intensity. As high performance camera has been equipped, the sedimentation images with high spatial and temporal resolution could be acquired, which can continuously capture sedimentation images with the resolution of 2048 × 2048 pixel at a maximum rate of 60 slides/s. All the pictures were processed to extract the luminance matrix top-down along the fixed vertical midline of each picture, which implied sedimentation characteristics of the system at the moment the picture was taken. Combining all the luminance matrixes along vertical middle lines of the pictures, a time-luminance matrix profile was obtained. Digital image processing techniques were used to eliminate interference and establish a three-dimensional surface model of the sedimentation dynamics. Then, the derivative mutation algorithm has been developed for the intelligent identification of sedimentation interface with threshold optimization so as to quantitatively analyze the sedimentation dynamics with visualization. The sedimentation curve and sedimentation dynamic equation of the non-homogeneous system were finally outputted by numerical fitting. The methodology was validated for great significance in determinations of small volume samples, parallel control multiple batches, and long period of time automatic measurement.

The effect of strain rate on the compaction properties of the non-steroidal anti-inflammatory drug ibuprofen has been studied using a compaction simulator. As the punch velocity was decreased there was an increase in the densification of the ejected compacts, a reduction in the limiting compact porosity and an increase in the maximum tensile strength of the compacts produced. These findings indicate that the consolidation mechanism was a balance between elastic and plastic deformation with the predominating mechanism governed by the punch velocity. At the faster two peak velocities investigated, the relationship between total axial recovery of the compacts and upper punch pressure was biphasic, whereas at the slowest peak velocity it was monophasic.

Many industrial powder systems are multicomponent and the use of powder fillers is widespread. This study reports on the measurement of the Young's modulus for four model binary powder mixtures,E(mix), and tests the application and predictive capability of published equations to experimental data. Powder blends of poly(tetrafluoroethylene) (PTFE) and lactose, PTFE and calcium carbonate, poly(vinylchloride) (PVC) and lactose, and PVC and calcium carbonate, representing two polymeric matrix powders and two powder fillers, were compressed to form beam specimens over a range of compositions and porosities. The Young's modulus of mixtures,E(mix), obtained from four-point-beam-bending studies was analysed to obtain values at zero porosity,E0(mix), which were fitted into published mixture equations. Results demonstrated that simple mixing rules did not hold. In all cases, negative deviations were obtained for plots ofE0(mix)versus volume % filler fraction, indicating that the polymeric powder components with the lower Young's modulus dominated theE0(mix) value. The Nielsen equation was found to be the preferred mixture relationship since, unlike other tested relationships, experimental data for all systems studied were well fitted by the function and predicted values ofE0(filler) showed reasonably good agreement with figures derived from monocomponent beam specimens.

Young's modulus of elasticity of organic drugs and excipients as determined by 3-point beam bending can be predicted from cohesive energy density. However, the moduli are lower than expected from theory due to specimen effects or to temperature differences between the theoretical treatment and measurements made at room temperature (i.e., compacted beams, 3-point beam bending). When experimentally determined single crystal elastic constants are used to calculate Young's modulus for a number of molecular solids, agreement between experiment and theory is improved. For Aspirin, there was good agreement between the lattice dynamic approach, the theoretical equation based on cohesive energy density and experimental measurements based on the flexure of compacted beams.

Lubricant film formation on sodium chloride particles by two commercial (A and B), and one high-purity sample of magnesium stearate (C) prepared in an acidic medium, has been studied. After mixing with 0.1 or 0.5 wt.% concentration of lubricant, the distribution on individual host particles was found to be non-uniform when assessed using imaging SIMS. For all samples, areas of high as well as low lubricant concentration were observed. Static SIMS spectra for sodium chloride and sodium chloride-magnesium stearate mixes have also been obtained. Positive and negativeion ratios were compared to interpret the spectra and identify the mechanism for lubricant film formation. The adsorption of lubricant molecules has been considered to be one of the most important mechanisms for excipient surface coverage. The observed Na+/Mg+ ratio of 521.11 for the uncoated excipient was reduced to 0.94, 1.25 and 13.36 after 2 min. mixing with 0.5 wt.% concentration of A, B and C respectively. Since adherence of lubricant particles to host particle surfaces was not found after this mixing period, these reductions indicated the formation of molecular layers on the sodium chloride particles. Also, as the ratio after mixing for C was much higher than for the other samples, a relatively incomplete molecular coverage was envisaged. The distribution of the lubricant on the excipient surface has been discussed with reference to its influence on lubrication and the implication on the properties of the finished product. The static SIMS spectra have also been compared to reflect the fundamental crystalline structures of these lubricants.

The surface energies of the interphases between the adsorbate nitrogen and the adsorbents microfine and microcrystalline celluloses were determined from adsorption isotherms at 77 K using the Polanyi phenomenological adsorption potential e 0 , the Dubinin—Radushkevich characteristic free energy E 0 and the adsorption coefficient of the Brunauer, Emmett and Teller equation. The surface area of three grades of microcrystalline and four grades of microfine cellulose were also measured. The various grades of microfine and microcrystalline cellulose, although produced with different physical dimensions, showed similar B.E.T. surface areas (S BET ). It was found that the Polanyi potential can be used to discriminate between celluloses formed by different methods, whereas the free energy calculated from the Dubinin—Radushkevich equation provides information about the mechanism of pore filling and hence about the surface topology.

A method has been developed for the frictional assessment of powder lubricants using a shear-box tester similar to that employed by Jenike. One commercial magnesium stearate, three high-purity magnesium stearates and three high-purity magnesium palmitates were assessed using this method. Powders with a well-ordered crystal structure and particle shape have a lower initial maximum coefficient of friction μa. The difference between μa and μb, the equilibrium dynamic friction coefficient, gives an indication of lubricant film-forming propensity. The basic friction equation is obeyed by the powders for most of the load range studied but deviates slightly approaching zero normal load.