Mechanical characterization of pharmaceutical solids: A comparison between rheological tests performed under static and dynamic porosity conditions (original) (raw)
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“Apparent” Young’s elastic modulus and radial recovery for some tableted pharmaceutical excipients
European Journal of Pharmaceutical Sciences, 2004
The effects of compact size and of powder particle size on the determination of "apparent" compressive Young's modulus of elasticity, E, were evaluated, for three pharmaceutical excipients (Microcrystalline cellulose, MCC, Calcium hydrogen phosphate dihydrate, CHPD, and pregelatinized starch, PGS) differing in deformational behaviour during compression. One-and two-compact (composite) specimens were employed and the equations of Spriggs [J. Am. Ceram. Soc. 44 (1961) 628] and Phani & Niyogi [J. Mater. Sci. 22 (1987) 257] were employed for prediction of E, at zero and 0.15 porosity (E 0 and E 0.15 ). It was found that E 0 and E 0.15 are affected by the particle size, in the case of PGS, but by the compact size and assembly in the case of MCC and CHPD. Reduction in E 0 and E 0.15 values for two-compact assembly corresponded to large and medium compact size only of MCC and CHPD, while specimen assembly was not affecting significantly the experimental data if small compacts of MCC and CHPD or any size compacts of PGS were used. The exponent f of the Phani and Niyogi equation has been considered as parameter of pore structure and particle morphology. It was significantly affected by the compact size of all the excipients, by the two-compact assembly of MCC and CHPD and by the particle size of CHPD and PGS. Absence of significant particle size effect on the parameter f, for the case of MCC is attributed to the elongated particle shape, while the highly significant one for the case of PGS is explained by the extensive elasto-plastic deformation during compression, which is greatly dependent on the grain size. Values of the % radial elastic recovery (%RR), at porosity 0 and 0.15, were determined and correlation of the experimental data was attempted to Young's modulus (E). A simple linear equation is proposed for prediction of Young's modulus, E, from %RR, at least in the porosity range between 0.1 and 0.3 (representative of commercial pharmaceutical tablets), but use of %RR instead to E is applicable only under many limitations.
EPJ Web of Conferences, 2017
In the pharmaceutical field, tablets are the most common dosage form for oral administration in the world. Among different manufacturing processes, direct compression is widely used because of its economics interest and it is a process which avoids the steps of wet granulation and drying processes. Tablets are composed of at least two ingredients: an active pharmaceutical ingredient (API) which is mixed with a diluent. The nature of the powders and the processing conditions are crucial for the properties of the blend and, consequently, strongly influence the mechanical characteristics of tablets. Moreover, tablets have to present a suitable mechanical strength to avoid crumbling or breaking when handling, while ensuring an appropriate disintegration after administration. Accordingly, this mechanical property is an essential parameter to consider. Experimental results showed that proportion of the diluent, fragmentary (DCPA) or plastic (MCC), had a large influence on the tensile strength evolution with API content as well as the compression load applied during tableting process. From these results a model was developed in order to predict the tensile strength of binary tablets by knowing the compression pressure. The validity of this model was demonstrated for the two studied systems and a comparison was made with two existing models.
International journal of pharmaceutics, 1999
Most of the pharmaceutical processes involved in the manufacturing of so lid dosage forms are connected with powder flow properties, at least for some of the intermediate steps. Powder flow characteristics are commonl y investigated by various measurements, such as handling angles, tap tes ting, shear cell measurements, etc. All these approaches allow the calc ulation of indices characterising powder flowability. Unfortunately, th ese methodologies are highly product consuming, which is a limitation in the first steps of a novel drug development, when only a small amount of product is available. The use of mercury porosimetry to evaluate compre ssibility and flow properties of powders could be a new and alternative approach to obtain insight in the rheological properties of granular med ium by the interpretation of the first part of programs (low pressures) . We have developed such an evaluation and compared the results obtaine d with those given by tap testing and shear cell measur...
The effect of mechanical strain on properties of lubricated tablets compacted at different pressures
Powder Technology, 2016
A full factorial design of experiments was used to study the effect of blend shear strain on the compaction process, relative density and strength of pharmaceutical tablets. The powder blends were subjected to different shear strain levels (integral of shear rate with respect to time) using an ad hoc Couette shear cell. Tablets were compressed at different compaction forces using an instrumented compactor simulator, and compaction curves showing the force-displacement profiles during compaction were obtained. Although the die-fill blend porosity (initial porosity) and the minimum in-die tablet porosity (at maximum compaction) decreased significantly with shear strain, the final tablet porosity was surprisingly independent of shear strain. The increase in the in-die maximum compaction with shear strain was, in fact, compensated during postcompaction relaxation of the tables, which also increased significantly with shear strain. Therefore, tablet porosity alone was not sufficient to predict tablet tensile strength. A decrease in the 'work of compaction' as a function of shear strain, and an increase in the recovered elastic work was observed, which suggested weaker particle-particle bonding as the shear strain increased. For each shear strain level, the Ryskewitch Duckworth equation was a good fit to the tensile strength as a function of tablet porosity, and the obtained asymptotic tensile strength at zero porosity exhibited a 60% reduction as a function of shear strain. This was consistent with a reduced bonding efficiency as the shear strain increased.
The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are compared to previously published values derived from terahertz (THz) refractive index data obtained from exactly the same tablet sample sets. It is shown that the elastic bulk modulus is dependent on API wt% loading under constant tablet preparation conditions delivering equal dimensions and porosity. The findings are considered of novel value in respect to establishing consistency of tablet production and optimisation of physical properties.
Tensile strength of tablets containing two materials with a different compaction behaviour
International journal of pharmaceutics, 2000
The tensile strength of tablets compressed from binary mixtures is in general not linearly related to the strength of tablets prepared from single materials; in many cases it shows a decreased tensile strength relative to interpolation. The materials used in this study, sodium chloride and pregelatinised starch, are both plastically deforming materials, but have a different densification and relaxation behaviour. The yield pressure of the binary mixtures shows an almost linear relationship. As an effect of their lower yield pressure, starch particles yield earlier than sodium chloride particles. The following enclosure prevents some sodium chloride particles to yield or crack. The relaxation of the tablets is higher than the relaxation calculated by linear interpolation of the relaxation behaviour of the two pure materials. The difference between the measured porosity expansion and the data obtained by linear interpolation can be considered as a measure for the reduced interparticle...
International journal of pharmaceutics, 2017
The physical properties and mechanical integrity of pharmaceutical tablets are of major importance when loading with active pharmaceutical ingredient(s) (API) in order to ensure ease of processing, control of dosage and stability during transportation and handling prior to patient consumption. The interaction between API and excipient, acting as functional extender and binder, however, is little understood in this context. The API indomethacin is combined in this study with microcrystalline cellulose (MCC) at increasing loading levels. Tablets from the defined API/MCC ratios are made under conditions of controlled porosity and tablet thickness, resulting from different compression conditions, and thus compaction levels. Mercury intrusion porosimetry is used to establish the accessible pore volume, pore size distribution and, adopting the observed region of elastic intrusion-extrusion at high pressure, an elastic bulk modulus of the skeletal material is recorded. Porosity values are ...
Drug Development and Industrial Pharmacy, 2010
Objective: The aim of this work is to study the effect of compaction on the specific surface area of tablets composed of various pharmaceutical materials (microcrystalline cellulose, lactose, and anhydrous calcium phosphate) compacted under seven degrees of compaction pressure. Methods: In a first part, the influence of the deformation behavior of the compacted materials on the evolution of the specific surface area is observed. In a second part, the brittle and ductile abilities of the materials are calculated using the specific surface area values. The experimental results are used to calculate the number and the force of interparticulate bonds inside the tablet. Results and Discussion: Tablets made of microcrystalline cellulose, which deform plastically, have specific surface areas that fall under pressure. In the case of lactose, the tablet specific surface area first increases to reach a maximum value at a pressure of 150 MPa. At higher pressure, however, the specific surface area decreases. The specific surface area of tablets composed of anhydrous calcium phosphate consistently increases, whatever the compaction pressure applied. Moreover, the evolution of the specific surface area is correlated with the tensile strength of the corresponding tablets. The number and the force of interparticulate bonds make it possible to classify the materials according to their deformation behavior and to quantify their ability to form cohesive tablets.
The elastic relaxation of starch tablets during ejection
Powder Technology, 2009
Tablets are invariably formed by uniaxial compression in rigid dies and the tablet mechanical integrity is highly dependent on its ability to withstand the physical dimensional changes resulting from the elastic relaxation due to the release of the elastic strains incurred during the tablet formation. Therefore, a complete understanding of the continuous tablet elastic relaxation behaviour will provide designers of the solid drug delivery system, important information on the probable mechanical performances of the designed tablets and the likelihood of failures at each stage in the tablet preparation process. This current work has successfully studied online Starch 1500 tablet elastic relaxation behaviour during ejection, which is one of the main stages in a tablet preparation through the use of novel non-contact laser measuring devices. The starch tablets were observed to undergo 'recompression' or height reduction in the early stages of ejection, followed by height expansion as they moved further towards the die exit and during emergence. Online diametrical measurements of the tablets during emergence indicated the existence of periodic diametrical expansions-contractions, which has been attributed to the diametrical elastic relaxation behaviour as well as the topographical nature of the circumferential tablet surface. The amplitudes of these expansioncontraction cycles, are believed to be dependent upon the corresponding stored elastic energy of that particular strip of circumferential surface in contact with the die walls. It is also found that the starch tablets formed at a lower compaction velocity predominantly dissipate the internal stored elastic energies by plastic flow and maintain its stored elastic energy during the ejection stage in relative to those formed at a higher compaction velocity.