The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
Agba D. Salman - One of the best experts on this subject based on the ideXlab platform.
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The effect of roller compaction and Tableting stresses on pharmaceutical Tablet performance
Powder Technology, 2019Co-Authors: Arthi D. Rajkumar, Gavin K. Reynolds, David Wilson, Stephen A.c. Wren, Agba D. SalmanAbstract:Abstract In this research the effect of two fundamental stresses, i.e. the Tableting load and roller compaction pressure, on Tablet Disintegration were investigated. Excipient materials were roller compacted using a range of pressures, and Tablets were produced by compressing the consequent granules at varying Tableting loads. For this study mannitol, a brittle and soluble material, and microcrystalline cellulose, a deformable and insoluble material, were investigated at varying binary ratios. The Tablets were characterised by analysis of the compactibility and a flow cell imaging method was utilised to investigate Tablet Disintegration in real-time. It was found that the effect of roller compaction (RC) pressure on Tablet tensile strength and porosity was dependent on the Tableting load used. At low Tableting load, the Tablet porosity varied depending on the RC pressure used, whereas the tensile strength was largely unaffected. The use of a high Tableting load leads to the opposite effect being observed. The tensile strength was highly dependent on the RC pressure used. In terms of the Tablet Disintegration the RC pressure did not influence the Disintegration behaviour when low Tableting loads were used as the process was rapid. When higher Tableting loads were used, Tablets containing granules roller compacted using lower pressure expanded in size larger than when a low RC pressure was used. A low RC pressure also lead to a faster particle release rate was observed.
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Investigating the effect of processing parameters on pharmaceutical Tablet Disintegration using a real-time particle imaging approach
European Journal of Pharmaceutics and Biopharmaceutics, 2016Co-Authors: Arthi D. Rajkumar, Stephen Wren, Gavin K. Reynolds, David Wilson, Michael J. Hounslow, Agba D. SalmanAbstract:Tablet Disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the Tablet will break up in vivo and that active drug will be available for absorption. Variations in Tablet properties cause variation in Disintegration behaviour. While the standardised pharmacopeial Disintegration test can show differences in the speed of Disintegration of different Tablets, it does not give any mechanistic information about the underlying cause of the difference. With quantifiable Disintegration data, and consequently an improved understanding into Tablet Disintegration, a more knowledge-based approach could be applied to the research and development of future Tablet formulations. The aim of the present research was to introduce an alternative method which will enable a better understanding of Tablet Disintegration using a particle imaging approach. A purpose-built flow cell was employed capable of online observation of Tablet Disintegration, which can provide information about the changing Tablet dimensions and the particles released with time. This additional information can improve the understanding of how different materials and process parameters affect Tablet Disintegration. Standard USP analysis was also carried out to evaluate and determine whether the flow cell method can suitably differentiate the Disintegration behaviour of Tablets produced using different processing parameters. Placebo Tablets were produced with varying ratios of insoluble and soluble filler (mannitol and MCC, respectively) so that the effect of variation in the formulation can be investigated. To determine the effect of the stress applied during granulation and Tableting on Tablet Disintegration behaviour, analysis was carried out on Tablets produced using granular material compressed at 20 or 50 bar, where a Tableting load of either 15 or 25 kN was used. By doing this the Tablet Disintegration was examined in terms of the Tablet porosity by monitoring the Tablet area and particle release. It was found that when 20 and 50 bar roller compaction pressure was used the USP analysis showed almost identical Disintegration times for the consequent Tablets. With the flow cell method a greater Tablet swelling was observed for the lower pressure followed by steady Tablet erosion. Additionally, more particles were released during Disintegration due to the smaller granule size distribution within the Tablet. When a higher Tableting pressure was applied the Tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower Tablet erosion and particle release were also observed, largely due to the Tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the Tablet porosity affects the Tablet Disintegration, whereby a more porous Tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that Tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and Tableting pressure used.
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A novel method to quantify Tablet Disintegration
Powder Technology, 2013Co-Authors: Xavier Mesnier, Michael J. Hounslow, Tim O. Althaus, Laurent Forny, Gerhard Niederreiter, Stefan Palzer, Agba D. SalmanAbstract:Abstract One of the aims in the food industry is to produce fast dissolving products. The dissolution of Tablets in water is often accompanied with Disintegration which is the process of breaking up the Tablet into smaller fragments. Disintegration increases the dissolution rate by increasing the surface area available for dissolution to occur. Such a process is helped by the use of disintegrants which are widely used in the pharmaceutical industry. The aim of this work is to investigate whether disintegrants could be introduced in a food system to improve the overall reconstitution of food powders. For this purpose, a food grade disintegrant was selected to be introduced into Tablets of maltodextrin which is a food model product. To provide further understanding of the Disintegration process, a novel characterization method has been developed. It combines the implementation of a new experimental setup based on a flow cell, where images of the Disintegration process are captured, together with the use of an image analysis programme. This approach allows the determination of both the Tablet dimensions and the size of the disintegrates, i.e. the particles released during Disintegration, with time. Such knowledge is important in identifying the stages of the reconstitution process when the disintegrant's action becomes effective. The results based on the system described above show that particles released in the presence of disintegrants are not only more important in number, but also their mean size is larger. This results in the fact that maltodextrin Tablets are reduced in size faster in presence of disintegrants, up to 20% in this case.
František Štěpánek - One of the best experts on this subject based on the ideXlab platform.
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Frequency analysis of stress relaxation patterns reveals the effect of formulation and process history on Tablet Disintegration
Powder Technology, 2021Co-Authors: Jan Tomas, Ondřej Dammer, Jakub Dvořák, František ŠtěpánekAbstract:Abstract Tablets are the most common pharmaceutical dosage form. Being compressed from smaller particles or granules, the Disintegration rate of Tablets in the gastro-intestinal tract is a key property that strongly influences the rate of drug release. While established methods for in vitro Tablet Disintegration measurement provide information about the final Disintegration time, a more detailed analysis of the Disintegration process can be a rich source of additional information. In this work, a new method of Tablet Disintegration monitoring based on real-time recording of stress relaxation curves in Tablets after immersion in the dissolution medium is presented. The signal is recorded using a texture analyzer with a needle probe, and then processed to reveal structural changes in the disintegrating Tablet. It is shown that the frequency and amplitude of fluctuations on the stress relaxation curve are uniquely able to capture parameters such as the disintegrant content and the particle size of the drug and excipients from which the Tablet was made. Moreover, the method is highly sensitive to variations in the composition of dissolution media; it can therefore be used during formulation development, biopharmaceutical analysis and for the general understanding of process-property relationships of compacted granular materials.
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Investigation of Tablet Disintegration pathways by the combined use of magnetic resonance imaging, texture analysis and static light scattering.
International journal of pharmaceutics, 2020Co-Authors: Jakub Dvořák, Jan Tomas, Marek Schöngut, Ondřej Dammer, Josef Beranek, Denisa Lizoňová, Tomas Pekarek, František ŠtěpánekAbstract:Efficient Tablet Disintegration is a pre-requisite for fast and complete drug dissolution from immediate release formulations. While the overall Tablet Disintegration time is a routinely measured quality attribute of pharmaceutical products, little attention is usually paid to the analysis of Disintegration fragments and the cascade of elementary steps that lead to their formation. In this work, we investigate the Disintegration pathways of directly compressed Tablets by a unique combination of three methods: (i) magnetic resonance imaging (MRI), to gain insight into structural changes of Tablets during Disintegration; (ii) texture analysis, to measure the Disintegration kinetics; and (iii) static light scattering, to characterise the size distribution of Disintegration fragments. By systematically varying the Tablet composition (50-90% of ibuprofen as a model active ingredient, 0-4% of croscarmellose sodium disintegrant, 6-50% of lactose monohydrate filler), a relationship between the Tablet formulation, the size distribution of the Disintegration fragments and the dissolution rate of the active ingredient has been established. To interpret the experimental observations, we analyse the Disintegration fragments by Raman mapping and relate their composition and structure to the micro-scale arrangement of individual formulation components inside the Tablet.
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Probing the early stages of Tablet Disintegration by stress relaxation measurement.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2018Co-Authors: Jan Tomas, Marek Schöngut, Ondřej Dammer, Josef Beranek, Aleš Zadražil, František ŠtěpánekAbstract:Abstract Rapid Tablet Disintegration is a requirement for the efficient dissolution of the active pharmaceutical ingredient (API) from immediate release Tablets. From the mechanistic viewpoint, Tablet Disintegration begins by the wetting of the Tablet surface and the ingress of dissolution medium into the Tablet pore structure, followed by the loosening of inter-particle bonds. The present work introduces a new methodology for probing and quantifying the early stages of Tablet Disintegration by stress relaxation measurements using texture analysis (TA). The method is based on applying a pre-defined load on the Tablet by means of a needle-shaped probe and measuring the Tablet resistance in time after the addition of the dissolution medium. This measurement provides information about the extent and rate of stress relaxation within the Tablet upon hydration. Using a Tablet formulation containing ibuprofen as the API and lactose as excipient, the effect of the API content, compaction pressure, and pH of the dissolution medium on the stress relaxation rate was systematically investigated. It is shown that using a dissolution medium pre-saturated by the formulation components has only a minor effect on the Tablet Disintegration rate compared to a pure phosphate buffer, meaning that the surface dissolution of particles within the Tablet is not the main pre-requisite of Disintegration in this case. On the other hand, pH of the dissolution medium was found to have a very strong effect on the stress relaxation rate in the Tablet after wetting, suggesting that van der Waals interactions rather than solid bridges are the predominant particle bonding mechanism in the investigated formulations.
Jan Tomas - One of the best experts on this subject based on the ideXlab platform.
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Frequency analysis of stress relaxation patterns reveals the effect of formulation and process history on Tablet Disintegration
Powder Technology, 2021Co-Authors: Jan Tomas, Ondřej Dammer, Jakub Dvořák, František ŠtěpánekAbstract:Abstract Tablets are the most common pharmaceutical dosage form. Being compressed from smaller particles or granules, the Disintegration rate of Tablets in the gastro-intestinal tract is a key property that strongly influences the rate of drug release. While established methods for in vitro Tablet Disintegration measurement provide information about the final Disintegration time, a more detailed analysis of the Disintegration process can be a rich source of additional information. In this work, a new method of Tablet Disintegration monitoring based on real-time recording of stress relaxation curves in Tablets after immersion in the dissolution medium is presented. The signal is recorded using a texture analyzer with a needle probe, and then processed to reveal structural changes in the disintegrating Tablet. It is shown that the frequency and amplitude of fluctuations on the stress relaxation curve are uniquely able to capture parameters such as the disintegrant content and the particle size of the drug and excipients from which the Tablet was made. Moreover, the method is highly sensitive to variations in the composition of dissolution media; it can therefore be used during formulation development, biopharmaceutical analysis and for the general understanding of process-property relationships of compacted granular materials.
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Investigation of Tablet Disintegration pathways by the combined use of magnetic resonance imaging, texture analysis and static light scattering.
International journal of pharmaceutics, 2020Co-Authors: Jakub Dvořák, Jan Tomas, Marek Schöngut, Ondřej Dammer, Josef Beranek, Denisa Lizoňová, Tomas Pekarek, František ŠtěpánekAbstract:Efficient Tablet Disintegration is a pre-requisite for fast and complete drug dissolution from immediate release formulations. While the overall Tablet Disintegration time is a routinely measured quality attribute of pharmaceutical products, little attention is usually paid to the analysis of Disintegration fragments and the cascade of elementary steps that lead to their formation. In this work, we investigate the Disintegration pathways of directly compressed Tablets by a unique combination of three methods: (i) magnetic resonance imaging (MRI), to gain insight into structural changes of Tablets during Disintegration; (ii) texture analysis, to measure the Disintegration kinetics; and (iii) static light scattering, to characterise the size distribution of Disintegration fragments. By systematically varying the Tablet composition (50-90% of ibuprofen as a model active ingredient, 0-4% of croscarmellose sodium disintegrant, 6-50% of lactose monohydrate filler), a relationship between the Tablet formulation, the size distribution of the Disintegration fragments and the dissolution rate of the active ingredient has been established. To interpret the experimental observations, we analyse the Disintegration fragments by Raman mapping and relate their composition and structure to the micro-scale arrangement of individual formulation components inside the Tablet.
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Probing the early stages of Tablet Disintegration by stress relaxation measurement.
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2018Co-Authors: Jan Tomas, Marek Schöngut, Ondřej Dammer, Josef Beranek, Aleš Zadražil, František ŠtěpánekAbstract:Abstract Rapid Tablet Disintegration is a requirement for the efficient dissolution of the active pharmaceutical ingredient (API) from immediate release Tablets. From the mechanistic viewpoint, Tablet Disintegration begins by the wetting of the Tablet surface and the ingress of dissolution medium into the Tablet pore structure, followed by the loosening of inter-particle bonds. The present work introduces a new methodology for probing and quantifying the early stages of Tablet Disintegration by stress relaxation measurements using texture analysis (TA). The method is based on applying a pre-defined load on the Tablet by means of a needle-shaped probe and measuring the Tablet resistance in time after the addition of the dissolution medium. This measurement provides information about the extent and rate of stress relaxation within the Tablet upon hydration. Using a Tablet formulation containing ibuprofen as the API and lactose as excipient, the effect of the API content, compaction pressure, and pH of the dissolution medium on the stress relaxation rate was systematically investigated. It is shown that using a dissolution medium pre-saturated by the formulation components has only a minor effect on the Tablet Disintegration rate compared to a pure phosphate buffer, meaning that the surface dissolution of particles within the Tablet is not the main pre-requisite of Disintegration in this case. On the other hand, pH of the dissolution medium was found to have a very strong effect on the stress relaxation rate in the Tablet after wetting, suggesting that van der Waals interactions rather than solid bridges are the predominant particle bonding mechanism in the investigated formulations.
Arthi D. Rajkumar - One of the best experts on this subject based on the ideXlab platform.
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The effect of roller compaction and Tableting stresses on pharmaceutical Tablet performance
Powder Technology, 2019Co-Authors: Arthi D. Rajkumar, Gavin K. Reynolds, David Wilson, Stephen A.c. Wren, Agba D. SalmanAbstract:Abstract In this research the effect of two fundamental stresses, i.e. the Tableting load and roller compaction pressure, on Tablet Disintegration were investigated. Excipient materials were roller compacted using a range of pressures, and Tablets were produced by compressing the consequent granules at varying Tableting loads. For this study mannitol, a brittle and soluble material, and microcrystalline cellulose, a deformable and insoluble material, were investigated at varying binary ratios. The Tablets were characterised by analysis of the compactibility and a flow cell imaging method was utilised to investigate Tablet Disintegration in real-time. It was found that the effect of roller compaction (RC) pressure on Tablet tensile strength and porosity was dependent on the Tableting load used. At low Tableting load, the Tablet porosity varied depending on the RC pressure used, whereas the tensile strength was largely unaffected. The use of a high Tableting load leads to the opposite effect being observed. The tensile strength was highly dependent on the RC pressure used. In terms of the Tablet Disintegration the RC pressure did not influence the Disintegration behaviour when low Tableting loads were used as the process was rapid. When higher Tableting loads were used, Tablets containing granules roller compacted using lower pressure expanded in size larger than when a low RC pressure was used. A low RC pressure also lead to a faster particle release rate was observed.
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Investigating the effect of processing parameters on pharmaceutical Tablet Disintegration using a real-time particle imaging approach
European Journal of Pharmaceutics and Biopharmaceutics, 2016Co-Authors: Arthi D. Rajkumar, Stephen Wren, Gavin K. Reynolds, David Wilson, Michael J. Hounslow, Agba D. SalmanAbstract:Tablet Disintegration is a fundamental parameter that is tested in vitro before a product is released to the market, to give confidence that the Tablet will break up in vivo and that active drug will be available for absorption. Variations in Tablet properties cause variation in Disintegration behaviour. While the standardised pharmacopeial Disintegration test can show differences in the speed of Disintegration of different Tablets, it does not give any mechanistic information about the underlying cause of the difference. With quantifiable Disintegration data, and consequently an improved understanding into Tablet Disintegration, a more knowledge-based approach could be applied to the research and development of future Tablet formulations. The aim of the present research was to introduce an alternative method which will enable a better understanding of Tablet Disintegration using a particle imaging approach. A purpose-built flow cell was employed capable of online observation of Tablet Disintegration, which can provide information about the changing Tablet dimensions and the particles released with time. This additional information can improve the understanding of how different materials and process parameters affect Tablet Disintegration. Standard USP analysis was also carried out to evaluate and determine whether the flow cell method can suitably differentiate the Disintegration behaviour of Tablets produced using different processing parameters. Placebo Tablets were produced with varying ratios of insoluble and soluble filler (mannitol and MCC, respectively) so that the effect of variation in the formulation can be investigated. To determine the effect of the stress applied during granulation and Tableting on Tablet Disintegration behaviour, analysis was carried out on Tablets produced using granular material compressed at 20 or 50 bar, where a Tableting load of either 15 or 25 kN was used. By doing this the Tablet Disintegration was examined in terms of the Tablet porosity by monitoring the Tablet area and particle release. It was found that when 20 and 50 bar roller compaction pressure was used the USP analysis showed almost identical Disintegration times for the consequent Tablets. With the flow cell method a greater Tablet swelling was observed for the lower pressure followed by steady Tablet erosion. Additionally, more particles were released during Disintegration due to the smaller granule size distribution within the Tablet. When a higher Tableting pressure was applied the Tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower Tablet erosion and particle release were also observed, largely due to the Tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the Tablet porosity affects the Tablet Disintegration, whereby a more porous Tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that Tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and Tableting pressure used.
Jean Paul Remon - One of the best experts on this subject based on the ideXlab platform.
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Vaginal distribution and retention of Tablets comprising starch-based multiparticulates: evaluation by colposcopy.
Drug development and industrial pharmacy, 2012Co-Authors: Samata Mehta, Jean Paul Remon, Hans Verstraelen, Leen Vandaele, Els Mehuys, Chris VervaetAbstract:We have developed fast-disintegrating Tablets comprising starch-based pellets and excipient granules for intravaginal drug delivery. The purpose of this study was to evaluate the intravaginal Disintegration, distribution and retention behavior of these Tablets in sheep and women using colposcopy as visualization technique. One Tablet was administered to each study subject (n = 6) and repeated colposcopy examination was performed over a 48 h and 24 h period in sheep and women, respectively. Colposcopy in sheep indicated that in vivo Tablet Disintegration was initiated within 30 min of vaginal administration and that due to Disintegration of the pellets themselves, the formulation was transformed into a gel-like mass which distributed throughout the entire vaginal cavity within 2–4 h. In vivo Tablet Disintegration after intravaginal administration to women was complete within 4 h, whereby the formulation gradually spread throughout the vaginal cavity as complete covering was observed after 12 and 24 h. The ...
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effect of maltodextrin and superdisintegrant in directly compressible powder mixtures prepared via co spray drying
European Journal of Pharmaceutics and Biopharmaceutics, 2008Co-Authors: Yves Gonnissen, Jean Paul Remon, Chris VervaetAbstract:Abstract The effect of maltodextrins and superdisintegrants on the Tablet properties was evaluated in directly compressible powders coprocessed via spray drying. Powder mixtures containing acetaminophen, mannitol, erythritol and different maltodextrin types were prepared via co-spray drying and physically mixed with crospovidone (6% w/w, Kollidon ® CL) in order to evaluate the influence of maltodextrin grade (amylose/amylopectin ratio) on powder hygroscopicity, flowability, density and compactability. In addition, different superdisintegrant types and grades (6% w/w) were co-spray dried to evaluate their effect on Tablet Disintegration time. Tablet Disintegration was affected by the amylose/amylopectin ratio of the maltodextrins. Tablets containing Glucidex ® 2 (1–5% amylose) had a longer Disintegration time compared to Glucidex ® 9 (20% amylose) (11.8 min versus 5.7 min) and Unipure DC (50–70% amylose) (1 min). The Disintegration time of Tablets containing a coprocessed superdisintegrant was long due to loss of superdisintegrant during processing (preferential depositing on the spray dryer wall) and was in the following order: Kollidon ® CL ® XL ® ® CL-M ® XL-10 = Ac-Di-Sol ® . A combination of acetaminophen, mannitol, erythritol, Glucidex ® 9 and Kollidon ® CL was selected for further formulation and process optimisation of co-spray dried powders intended for direct compression.
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compaction of enteric coated pellets influence of formulation and process parameters on Tablet properties and in vivo evaluation
European Journal of Pharmaceutical Sciences, 2004Co-Authors: Ann Debunne, Chris Vervaet, Debby Mangelings, Jean Paul RemonAbstract:Abstract The aim of this study was to investigate the influence of formulation and compression parameters on the properties of Tablets, containing enteric-coated pellets, and on the integrity of the enteric polymer of the individual pellets after compression. In addition the piroxicam plasma concentrations were determined after single and multiple oral administration of powder, pellet and Tablet formulations at a dose of 0.3 mg piroxicam/kg bodyweight to dogs. Tablets consisted of enteric-coated pellets (containing 2.5% (w/w) piroxicam in combination with microcrystalline cellulose and sodium carboxymethylcellulose (using Avicel® PH 101 and Avicel® CL 611 in a ratio of 1–3)), cushioning waxy pellets and 10% Kollidon® CL (as an external disintegrator). From the D-optimality experimental design it was concluded that the ratio of coated pellets to cushioning pellets (CoP/CuP) affected all Tablet properties evaluated. Variation of the pellet size and the CoP/CuP ratio resulted in different in vitro Tablet Disintegration times. Enteric coating of the pellets or compression of the coated pellets did not have a significant influence (P>0.05) on AUC0→72 h. Cmax values obtained after oral administration of coated pellets and compressed coated pellets were significantly lower than for the other formulations. Differences in in vitro Tablet Disintegration times were not reflected in the onset of the piroxicam plasma concentrations. A dosing interval of 48 h prevented piroxicam accumulation following multiple dose administration.