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Jouko Yliruusi - One of the best experts on this subject based on the ideXlab platform.
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Spectroscopic insight for Tablet Compression.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2014Co-Authors: Satu Lakio, Osmo Antikainen, H Ylinara, Heikki Räikkönen, Jouko YliruusiAbstract:Tablet Compression process has been studied over the years from various perspectives. However what exactly happens to material during Compression is still unknown. In this study a novel Compression die which enables real-time spectroscopic measurements during the Compression of material is represented. Both near infrared and Raman spectroscope probes can be attached to the die. In this study the usage of the die is demonstrated by using Raman spectroscopy. Eicosane, d-glucose anhydrate, α-lactose monohydrate and xylitol were used in the study because their Compression behavior and bonding properties during Compression were assumed to be different. The intensity of the Raman signal changed during Compression with all of the materials. However, the intensity changes were different within the materials. The biggest differences were within the xylitol spectra. It was noticed that some peaks disappeared with higher Compression pressures indicating that the pressure affected variously on different bonds in xylitol structure. These reversible changes were supposed to relate the changes in conformation and crystal structure. As a conclusion, the die was found to be a significant addition for studying Compression process in real-time. It can help to reveal Process induced transformations (PITs) occurring during powder compaction.
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Direct Compression of Cellulose and Lignin Isolated by a New Catalytic Treatment
AAPS PharmSciTech, 2013Co-Authors: Anna Penkina, Osmo Antikainen, Jouko Yliruusi, Maija Hakola, Sirpa Vuorinen, Timo Repo, Peep Veski, Karin Kogermann, Jyrki HeinämäkiAbstract:Tablet Compression of softwood cellulose and lignin prepared by a new catalytic oxidation and acid precipitation method were investigated and compared with the established pharmaceutical direct Compression excipients. Catalytic pretreated softwood cellulose (CPSC) and lignin (CPSL) were isolated from pine wood (Pinus sylvestris). The compaction studies were carried out with an instrumented eccentric Tablet machine. The plasticity and elasticity of the materials under Compression were evaluated using force-displacement treatment and by determining characteristic plasticity (PF) and elasticity (EF) factors. With all biomaterials studied, the PF under Compression decreased exponentially as the Compression force increased. The Compression force applied in Tablet Compression did not significantly affect the elasticity of CPSC and microcrystalline cellulose (MCC) while the EF values for softwood lignins increased as Compression force increased. CPSL was clearly a less plastically deforming and less compactable material than the two celluloses (CPSC and MCC) and hardwood lignin. CPSL presented deformation and compaction behaviour almost identical to that of lactose monohydrate. In conclusion, the direct Tablet Compression behaviour of native lignins and celluloses can greatly differ from each other depending on the source and isolation method used.
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Effects of moisture on Tablet Compression of chitin
Carbohydrate Polymers, 2011Co-Authors: Viviana García Mir, Osmo Antikainen, Jyrki Heinämäki, Sari Airaksinen, Antonio Iraizoz Colarte, Milja Karjalainen, Ofelia Bilbao Revoredo, Olga Maria Nieto, Jouko YliruusiAbstract:Abstract Direct Compression of chitin was studied with special reference to the effects of moisture content on Tablet formation and properties. Two cellulosic direct Compression materials, microcrystalline cellulose (MCC) and spray-dried lactose-cellulose (SDLC, (Cellactose ® ) were used as reference materials. The compaction studies were carried out using an instrumented single-punch Tablet machine. For physical material characterisation, water sorption isotherms were determined gravimetrically and the effects of moisture on the solid-state properties were studied by means of FT-NIR spectroscopy and X-ray powder diffractometry (XRPD). The sorption isotherms showed that the moisture sorption capacity of chitin is clearly higher than that of SDLC and only slightly higher than that of MCC, especially in the high humidity range. The maximum crushing strength for the chitin Tablets was obtained at the moisture content ranging from 7% to 9%, approximately double the corresponding monolayer moisture content ( m o ). Lower and higher humidity levels clearly reduced the mechanical strength of the Tablets. It was also found that the elasticity and plasticity factors of chitin, MCC and SDLC were strongly dependent on the level of moisture present during compaction.
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New insights into segregation during Tabletting.
International Journal of Pharmaceutics, 2010Co-Authors: Satu Lakio, Osmo Antikainen, Heikki Räikkönen, Simo Siiriä, Sari Airaksinen, Tero Närvänen, Jouko YliruusiAbstract:The aim of this study was to evaluate how different granule size distributions affect the Tablet Compression process. The emphasis was on developing new analytic methods for Compression data for entire batch. In all, 18 batches of granules containing theophylline and lactose were Tabletted, using an instrumented eccentric Tabletting machine. During Tablet Compression, upper and lower punch forces were recorded. Mathematical methods were developed for analysing the Compression data during Tabletting. The results suggested two types of undulation in the Tabletting data: (1) short-time scale variation or Tablet-to-Tablet changes in force data and (2) long-time scale undulation describing the changes occurring throughout the Tabletting process, such as segregation. These undulation phenomena were analysed, using various mathematical methods. In addition the results suggest that smaller particles have better Tabletting properties, to a certain limit. However particle size alone cannot explain the Tabletability of granules.
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New Parameters Derived from Tablet Compression Curves. Part II. Force-Displacement Curve
Drug Development and Industrial Pharmacy, 1997Co-Authors: Osmo Antikainen, Jouko YliruusiAbstract:AbstractPreviously, many authors have described different types of parameters derived from Tablet Compression force-time curves. In this study, a great number of new Compression parameters were calculated from Tablet force-displacement curves. Tablets were made with an instrumented eccentric Tablet machine using three different Compression forces and three Compression speeds, and α-lactose monohydrate as a model material. The results showed that the presented new force-displacement parameters explain the Compression phenomenon from different points of view. The final usefulness of these parameters together should be studied in the future with different types of materials. It is expected that many of the presented parameters can give valuable information on Tablet Compression and can lay the foundation for understanding of the Compression phenomenon and bond formation during Tableting
Osmo Antikainen - One of the best experts on this subject based on the ideXlab platform.
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Spectroscopic insight for Tablet Compression.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2014Co-Authors: Satu Lakio, Osmo Antikainen, H Ylinara, Heikki Räikkönen, Jouko YliruusiAbstract:Tablet Compression process has been studied over the years from various perspectives. However what exactly happens to material during Compression is still unknown. In this study a novel Compression die which enables real-time spectroscopic measurements during the Compression of material is represented. Both near infrared and Raman spectroscope probes can be attached to the die. In this study the usage of the die is demonstrated by using Raman spectroscopy. Eicosane, d-glucose anhydrate, α-lactose monohydrate and xylitol were used in the study because their Compression behavior and bonding properties during Compression were assumed to be different. The intensity of the Raman signal changed during Compression with all of the materials. However, the intensity changes were different within the materials. The biggest differences were within the xylitol spectra. It was noticed that some peaks disappeared with higher Compression pressures indicating that the pressure affected variously on different bonds in xylitol structure. These reversible changes were supposed to relate the changes in conformation and crystal structure. As a conclusion, the die was found to be a significant addition for studying Compression process in real-time. It can help to reveal Process induced transformations (PITs) occurring during powder compaction.
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Direct Compression of Cellulose and Lignin Isolated by a New Catalytic Treatment
AAPS PharmSciTech, 2013Co-Authors: Anna Penkina, Osmo Antikainen, Jouko Yliruusi, Maija Hakola, Sirpa Vuorinen, Timo Repo, Peep Veski, Karin Kogermann, Jyrki HeinämäkiAbstract:Tablet Compression of softwood cellulose and lignin prepared by a new catalytic oxidation and acid precipitation method were investigated and compared with the established pharmaceutical direct Compression excipients. Catalytic pretreated softwood cellulose (CPSC) and lignin (CPSL) were isolated from pine wood (Pinus sylvestris). The compaction studies were carried out with an instrumented eccentric Tablet machine. The plasticity and elasticity of the materials under Compression were evaluated using force-displacement treatment and by determining characteristic plasticity (PF) and elasticity (EF) factors. With all biomaterials studied, the PF under Compression decreased exponentially as the Compression force increased. The Compression force applied in Tablet Compression did not significantly affect the elasticity of CPSC and microcrystalline cellulose (MCC) while the EF values for softwood lignins increased as Compression force increased. CPSL was clearly a less plastically deforming and less compactable material than the two celluloses (CPSC and MCC) and hardwood lignin. CPSL presented deformation and compaction behaviour almost identical to that of lactose monohydrate. In conclusion, the direct Tablet Compression behaviour of native lignins and celluloses can greatly differ from each other depending on the source and isolation method used.
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Effects of moisture on Tablet Compression of chitin
Carbohydrate Polymers, 2011Co-Authors: Viviana García Mir, Osmo Antikainen, Jyrki Heinämäki, Sari Airaksinen, Antonio Iraizoz Colarte, Milja Karjalainen, Ofelia Bilbao Revoredo, Olga Maria Nieto, Jouko YliruusiAbstract:Abstract Direct Compression of chitin was studied with special reference to the effects of moisture content on Tablet formation and properties. Two cellulosic direct Compression materials, microcrystalline cellulose (MCC) and spray-dried lactose-cellulose (SDLC, (Cellactose ® ) were used as reference materials. The compaction studies were carried out using an instrumented single-punch Tablet machine. For physical material characterisation, water sorption isotherms were determined gravimetrically and the effects of moisture on the solid-state properties were studied by means of FT-NIR spectroscopy and X-ray powder diffractometry (XRPD). The sorption isotherms showed that the moisture sorption capacity of chitin is clearly higher than that of SDLC and only slightly higher than that of MCC, especially in the high humidity range. The maximum crushing strength for the chitin Tablets was obtained at the moisture content ranging from 7% to 9%, approximately double the corresponding monolayer moisture content ( m o ). Lower and higher humidity levels clearly reduced the mechanical strength of the Tablets. It was also found that the elasticity and plasticity factors of chitin, MCC and SDLC were strongly dependent on the level of moisture present during compaction.
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New insights into segregation during Tabletting.
International Journal of Pharmaceutics, 2010Co-Authors: Satu Lakio, Osmo Antikainen, Heikki Räikkönen, Simo Siiriä, Sari Airaksinen, Tero Närvänen, Jouko YliruusiAbstract:The aim of this study was to evaluate how different granule size distributions affect the Tablet Compression process. The emphasis was on developing new analytic methods for Compression data for entire batch. In all, 18 batches of granules containing theophylline and lactose were Tabletted, using an instrumented eccentric Tabletting machine. During Tablet Compression, upper and lower punch forces were recorded. Mathematical methods were developed for analysing the Compression data during Tabletting. The results suggested two types of undulation in the Tabletting data: (1) short-time scale variation or Tablet-to-Tablet changes in force data and (2) long-time scale undulation describing the changes occurring throughout the Tabletting process, such as segregation. These undulation phenomena were analysed, using various mathematical methods. In addition the results suggest that smaller particles have better Tabletting properties, to a certain limit. However particle size alone cannot explain the Tabletability of granules.
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New Parameters Derived from Tablet Compression Curves. Part II. Force-Displacement Curve
Drug Development and Industrial Pharmacy, 1997Co-Authors: Osmo Antikainen, Jouko YliruusiAbstract:AbstractPreviously, many authors have described different types of parameters derived from Tablet Compression force-time curves. In this study, a great number of new Compression parameters were calculated from Tablet force-displacement curves. Tablets were made with an instrumented eccentric Tablet machine using three different Compression forces and three Compression speeds, and α-lactose monohydrate as a model material. The results showed that the presented new force-displacement parameters explain the Compression phenomenon from different points of view. The final usefulness of these parameters together should be studied in the future with different types of materials. It is expected that many of the presented parameters can give valuable information on Tablet Compression and can lay the foundation for understanding of the Compression phenomenon and bond formation during Tableting
Tim Kramer - One of the best experts on this subject based on the ideXlab platform.
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Tablet Compression force as a process analytical technology pat 100 inspection and control of Tablet weight uniformity
Journal of Pharmaceutical Sciences, 2019Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim KramerAbstract:The modern rotary pharmaceutical Tablet press is capable of accepting or rejecting individual Tablets based on the measured Compression force of the Tablet. Because during steady operation, each Tablet is compressed to the same thickness, a larger Compression force implies a heavier Tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured Compression force thus becomes an important input to the overall control strategy, and variability in the Compression force from one Tablet to the next corresponds directly with the uniformity of dosage units. This provides an extraordinary opportunity to use the instantaneous Compression force signal as a process analytical technology to make product collection decisions on every individual Tablet. Only 1 question requires investigation: how to set the main Compression force limits to achieve the desired Tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.
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Tablet Compression Force as a Process Analytical Technology (PAT): 100% Inspection and Control of Tablet Weight Uniformity
Journal of Pharmaceutical Sciences, 2018Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim KramerAbstract:Abstract The modern rotary pharmaceutical Tablet press is capable of accepting or rejecting individual Tablets based on the measured Compression force of the Tablet. Since during steady operation, each Tablet is compressed to the same thickness, a larger Compression force implies a heavier Tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured Compression force thus becomes an important input to the overall control strategy, and variability in the Compression force from one Tablet to the next corresponds directly with the uniformity of dosage units (UDU). This provides an extraordinary opportunity to use the instantaneous Compression force signal as a process analytical technology (PAT) to make product collection decisions on every individual Tablet. Only one question requires investigation: how to set the main Compression force limits to achieve the desired Tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.
Jon Hilden - One of the best experts on this subject based on the ideXlab platform.
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Tablet Compression force as a process analytical technology pat 100 inspection and control of Tablet weight uniformity
Journal of Pharmaceutical Sciences, 2019Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim KramerAbstract:The modern rotary pharmaceutical Tablet press is capable of accepting or rejecting individual Tablets based on the measured Compression force of the Tablet. Because during steady operation, each Tablet is compressed to the same thickness, a larger Compression force implies a heavier Tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured Compression force thus becomes an important input to the overall control strategy, and variability in the Compression force from one Tablet to the next corresponds directly with the uniformity of dosage units. This provides an extraordinary opportunity to use the instantaneous Compression force signal as a process analytical technology to make product collection decisions on every individual Tablet. Only 1 question requires investigation: how to set the main Compression force limits to achieve the desired Tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.
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Tablet Compression Force as a Process Analytical Technology (PAT): 100% Inspection and Control of Tablet Weight Uniformity
Journal of Pharmaceutical Sciences, 2018Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim KramerAbstract:Abstract The modern rotary pharmaceutical Tablet press is capable of accepting or rejecting individual Tablets based on the measured Compression force of the Tablet. Since during steady operation, each Tablet is compressed to the same thickness, a larger Compression force implies a heavier Tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured Compression force thus becomes an important input to the overall control strategy, and variability in the Compression force from one Tablet to the next corresponds directly with the uniformity of dosage units (UDU). This provides an extraordinary opportunity to use the instantaneous Compression force signal as a process analytical technology (PAT) to make product collection decisions on every individual Tablet. Only one question requires investigation: how to set the main Compression force limits to achieve the desired Tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.
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Evaluation of Small-Scale Powder Flow Characterization Tests in the Prediction of Large-Scale Process Failures
Journal of Pharmaceutical Innovation, 2016Co-Authors: Aaron Zettler, Aktham Aburub, Michael Koenig, Christopher Breslin, Matthew Allgeier, Phenil Patel, Jon Hilden, Biplob MitraAbstract:In pharmaceutical development, powder flow characteristics are notoriously difficult to predict. Although tests exist that aim to determine the flowability of powders, many have not been definitively correlated with a powder’s performance in downstream processes. Part of the challenge is that powder flow must occur over a broad range of consolidating stresses, including low-stress flow regimes such as the filling of a die cavity in a Tablet press and high-stress flow regimes such as the deformation associated with Tablet Compression. The objective of this work was to characterize several placebo formulations utilizing a variety of standardized and non-standardized experiments and contrasting those results with downstream Tablet Compression performance. Angle of repose, bulk and tap density, Hausner ratio, Carr’s compressibility index, a visual powder flow assessment, a mass flow rate test, Flodex, and powder shear testing were evaluated on several different blends of placebo powders to determine a predictive test for downstream process performance. The placebo powders consisted of a standard base unit formula, mixed with various levels of four different “pseudo-active pharmaceutical ingredients (APIs)” (i.e., excipients that mimic poorly flowing active pharmaceutical ingredients). All formulations were evaluated by the individual flow tests and then compressed on a rotary Tablet press. Formulations were deemed failures if the relative standard deviation of Tablet weight was >2 %, material stuck to punches (low lubrication), or exhibited ejection forces high enough to trigger automatic shutdown of Tablet press. The 2 % RSD limit is based on internally developed best practices for transferring Tablet Compression processes from development into manufacturing. The results of the Tablet Compression process were then compared to the results of the flowability tests to detect any correlations. The Hausner ratio and powder shear test results discriminated marginally between successful and failed batches and were highly correlated with each other.
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Prediction of roller compacted ribbon solid fraction for quality by design development
Powder Technology, 2011Co-Authors: Jon Hilden, Gretchen EarleAbstract:Abstract A current focus of the pharmaceutical industry drug development process is to incorporate mathematical modeling as part of a Quality by Design (QBD) development strategy. In support of this effort, a simple yet robust model is provided to control the solid fraction (a.k.a. relative density) of ribbons produced during a roller compaction unit operation. An equation is provided to calculate the stress applied to the ribbon as a function of the roll force, radius, and width. While roller compaction is considered as a plane-strain deformation process (ribbons become thinner and longer, but not wider), the calculated stress is provided as an equivalent value relevant to a uniaxial-strain deformation process such as Tablet Compression (i.e. Tablets become shorter, but not thicker or wider). The ‘equivalent stress’ thus provides a mechanism to compare roller compaction stresses with Tablet Compression stresses and associated solid fractions. Specifically, the ribbon solid fraction will equal the Tablet solid fraction when the applied equivalent stress matches the applied Tabletting stress. In this work, the equivalent stress equation is derived as a combination of basic physics and trending of historical measured roll stress profiles from various published sources. The model is then applied to new experimental data by comparing ribbon solid fractions to Tablet solid fractions at various stresses and for various formulations.
Leo Manley - One of the best experts on this subject based on the ideXlab platform.
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Tablet Compression force as a process analytical technology pat 100 inspection and control of Tablet weight uniformity
Journal of Pharmaceutical Sciences, 2019Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim KramerAbstract:The modern rotary pharmaceutical Tablet press is capable of accepting or rejecting individual Tablets based on the measured Compression force of the Tablet. Because during steady operation, each Tablet is compressed to the same thickness, a larger Compression force implies a heavier Tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured Compression force thus becomes an important input to the overall control strategy, and variability in the Compression force from one Tablet to the next corresponds directly with the uniformity of dosage units. This provides an extraordinary opportunity to use the instantaneous Compression force signal as a process analytical technology to make product collection decisions on every individual Tablet. Only 1 question requires investigation: how to set the main Compression force limits to achieve the desired Tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.
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Tablet Compression Force as a Process Analytical Technology (PAT): 100% Inspection and Control of Tablet Weight Uniformity
Journal of Pharmaceutical Sciences, 2018Co-Authors: Leo Manley, Jon Hilden, Pablo Valero, Tim KramerAbstract:Abstract The modern rotary pharmaceutical Tablet press is capable of accepting or rejecting individual Tablets based on the measured Compression force of the Tablet. Since during steady operation, each Tablet is compressed to the same thickness, a larger Compression force implies a heavier Tablet. Tablets that are too heavy likely contain more than the desired content of drug substance. The measured Compression force thus becomes an important input to the overall control strategy, and variability in the Compression force from one Tablet to the next corresponds directly with the uniformity of dosage units (UDU). This provides an extraordinary opportunity to use the instantaneous Compression force signal as a process analytical technology (PAT) to make product collection decisions on every individual Tablet. Only one question requires investigation: how to set the main Compression force limits to achieve the desired Tablet weights? In this work, a small-scale characterization method and associated mathematical model are developed to answer this question.