Pore shape in the sodium chloride matrix of tablets after the addition of starch as a second component (original) (raw)
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1 Characterisation of Pore Structures of 1 Pharmaceutical Tablets : A Review 2
2018
25 Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on 26 the design of a specific microstructure for the drug delivery system. However, the compaction process 27 particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical 28 tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of 29 oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the 30 dissolution process. In future, additive manufacturing is a potential game changer to design the inner 31 structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is 32 most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to 33 consider other parameters to fully resolve the interplay between microstructure and dosage form 34 performance. Specifically, tortuosit...
Pore size distribution in tablets measured with a morphological sieve
International Journal of Pharmaceutics, 2007
Porosity and pore structure are important characteristics of tablets, since they influence mechanical strength and many other properties. This paper proposes an alternative method for the characterization of pore structure based on image analysis of SEM micrographs. SEM images were made of sodium chloride tablets made with three different particle sizes. The pore size distribution in these images was determined with a technique referred to as a morphological sieve. The results were compared to the pore size distributions as obtained with mercury porosimetry. The SEM images display small cracks inside the grains and small 'floating' grains inside the pore space. As these artifacts are induced in sample preparation, they need to be identified and removed from the images before analysis. The influence of the size of the discarded structures on the total porosity and the pore size distribution was investigated. The small 'floating' grains prevented the determination of the size of large pores, but had a negligible effect on the porosity. The removal of small cracks inside the grains had no effect on the pore size distribution but a large effect on the porosity. Based on the comparison of these results with the experimentally determined porosity, a maximum size for the structures that were to be removed was determined. The resulting pore size distributions were in the same order of magnitude as the results obtained with mercury porosimetry. Both methods display a comparable relative shift of the pore size distributions to larger sizes for tablets with increasing particle size. Therefore, it can be concluded this image analysis technique is a good method for the characterization of pore structure.
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...
Location-Dependent Analysis of Porosity and Pore Direction in Tablets
Pharmaceutical Research, 2005
Purpose. Several phenomena in tablets indicate that an inhomogeneous pore distribution is formed during the compaction process. Examples are lamination and the capping of corners. In order to gain an understanding of the relation between structure and compact properties, analyzing the structure in a location dependent manner would be extremely useful. Our aim was to visualize and to quantitatively analyze the pore distribution in compacts.
Characterisation of pore structures of pharmaceutical tablets: A review
International Journal of Pharmaceutics
Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed.
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.
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 ...
The mechanical properties of model-compacted tablets
Journal of Materials Science, 2008
In this study, the compressive strength of tablets made with salt, starch and fat was investigated. The strength was found to increase with compaction pressure, up to a maximum value where further increase in the compaction pressure led to no increase in the strength. The maximum strength corresponded to the point where zero porosity was obtained during the compaction process. However, because of the elastic rebound of the tablets after ejection, the maximum strength corresponded to non-zero final tablet porosities which varied between the materials. For this reason, the use of the density occurring during the compaction process appeared to provide a more reliable comparison between the materials. A simple linear mixing rule did not hold in characterising the strength in the salt:starch:fat systems. However, two regimes were observed depending on the salt volume fraction. At low salt volume fractions, the effect of the salt was negligible. After a certain critical salt volume fraction, increasing the salt led to an increase in the strength. Finite element simulations based on X-ray microtomography images of the tablets suggested that in the first regime, the stresses due to the salt particles were localised but in the second regime, stress-bearing networks were formed between the salt particles.
Porosity parameters of lactose, glucose and mannitol tablets obtained by mercury porosimetry
International Journal of Pharmaceutics, 1996
The effect of compression force, compression speed and the amount of granulation liquid on the porosity parameters determined from lactose, glucose and mannitol tablets by high-pressure mercury porosimetry was investigated. Compression force affected all parameters measured, except the total pore surface area of lactose tablets. The changes in tablet microstructure with increasing compression force were particularly well detected from the pore volume size distributions of tablets. Compression speed affected the total pore volume of lactose tablets, both mean and median pore diameters of lactose tablets and mannitol tablets compressed from granules produced with a low amount of liquid, and the median pore diameter of glucose tablets. The compression speed dependence of these parameters was a sign of the time-dependent deformation of materials during compression. The amount of granulation liquid affected the total pore surface area of lactose and mannitol tablets. With a high amount of liquid, the surface area of pores was greater. The mean pore size of all tablets and the median pore diameter of mannitol tablets were smaller when a high amount of granulation liquid was used. Even when compressed with a high force, the pore volume size distributions of mannitol tablets with a low amount of granulation liquid were broader and the maxima were at larger pore diameters. It was concluded that each porosity parameter measured characterised the pore structure of compressed tablets from a different aspect. Thus, the use of all porosity parameters proved to be useful.
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.