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At least 19 recordsLinked to original sources
PubMed2004

Simulation of roller compaction using a laboratory scale compaction simulator.

A method for simulation of the roller compaction process using a laboratory scale compaction simulator was developed. The simulation was evaluated using microcrystalline cellulose as model material and ribbon solid fraction and tensile strength as key ribbon properties. When compacted to the same solid fractions, real and simulated ribbons exhibited similar compression behavior and equivalent mechanical properties (tensile strengths). Thus, simulated and real ribbons are expected to result in equivalent granulations. Although the simulation cannot account for some roller compaction aspects (non-homogeneous ribbon density and material bypass) it enables prediction of the effects that critical parameters such as roll speed, pressure and radius have on the properties of ribbons using a fraction of material required by conventional roller compaction equipment. Furthermore, constant ribbon solid fraction and/or tensile strength may be utilized as scale up and transfer factors for the roller compaction process. The improved material efficiency and product transfer methods could enable formulation of tablet dosage forms earlier in drug product development.

Cellulose↗
PubMed2026

A correction factor for bridging compaction simulator and different roller compactors.

Roller compaction (RC) is an important dry granulation technique. Since pilot and commercial scale roller compactors, which operate continuously on a large scale, usually require kilograms of material per run, formulation and process development directly on such roller compactors is not practical. In contrast, a compaction simulator (CS) can produce ribblets, also known as "slugs", using only a few grams of material with sinusoidal displacement profile replicating the motion of a specific point on the roll surface. Thus, it is possible to develop RC formulation and process in laboratory using a CS-based material-sparing approach. However, because of the inherently different configurations for applying pressure between die compression and roll compression, translating uniaxial pressure from CS experiments to roll pressure during RC is often unreliable, leading to significant uncertainties in the critical quality attributes of ribbons, such as ribbon solid fraction (or porosity) and mechanical strength. The objective of this study was to identify a correction factor (Kp = uniaxial die compression pressure/roll pressure), by correlating the compressibility profiles from CS and a roller compactor of interest, to enable more reliable process translation from CS to roller compactor. In this study, a Kp value of 0.5 was determined for Alexanderwerk WP120 and validated for Gerteis Mini-Pactor and Bepex Pharmapactor. This value may serve as a starting point for translating the optimal compaction pressure identified based on CS investigation to common roller compactors, requiring only minor adjustments to attain optimal RC process parameters (i.e., roll force and roll gap) for a chosen roller compactor.

Drug Compounding↗
PubMed1993

Calibration of a compaction simulator for the measurement of tablet thickness during compression.

For the calibration of a compaction simulator for punch displacement measurements, the displacement of the punch must be related to the voltage output of a linear variable displacement transducer (LVDT) which is attached to the punch via its movable core, with correction for any deformation of the machine parts which are inherently incorporated in the LVDT readings. Contrary to common assumptions the relationship between the displacement of the movable core and the voltage output of the LVDTs used is not linear. Similarly, the deformation of the machine parts did not follow Hooke's law of linear elasticity but exhibited characteristics of nonlinear elasticity. The data demonstrate the need for careful validation of the calibration of a compaction simulator when accurate punch displacements are required.

Calibration↗
PubMed1994

The role of the displacement-time waveform in the determination of Heckel behaviour under dynamic conditions in a compaction simulator and a fully-instrumented rotary tablet machine.

The Heckel equation has been used widely to characterize the compression behaviour of pharmaceutical powders, yet very little attention has been paid to the role of the displacement-time profile used to generate this relationship. The objective of this study was to evaluate and compare selected standard waveforms with actual and theoretical tablet press waveforms in the Heckel analysis of representative formulations under dynamic conditions in a compaction simulator and to compare such data with that determined on the same formulation using an actual fully-instrumented rotary tablet press. Increased tableting rate and different programmed displacement-time waveforms with the same gross punch-speed changed the Heckel behaviour of all formulations. The results of this study suggest the pressure-volume relationship determined during powder-bed compression is affected by the instantaneous punch-speed profile of the displacement-time waveform for all materials studied, even though they deform by different mechanisms. It appears that the instantaneous punch-speed profile of the particular displacement-time waveform is a confounding factor of Heckel analysis. Compaction simulators programmed to deliver saw-toothed displacement-time traces have the advantage of constant punch-speed and may be a better choice for characterizing a formulation by Heckel indices and the strain-rate sensitivity index. On the other hand, they also carry the liability of not being a realistic representation of tableting on a rotary tablet press.

Calcium Phosphates↗
PubMed2004

Modeling of adhesion in tablet compression. II. Compaction studies using a compaction simulator and an instrumented tablet press.

Adhesion problems are usually not identified until prolonged compression runs are studied near the end of the drug development process. During tablet manufacturing, adhesion problems encountered are usually addressed by statistically designed experiments based on experience. It would be a significant benefit for the pharmaceutical industry if adhesion problems could be identified early in drug development based on molecular considerations of the drug substance and/or prototype formulations. Drug substance-punch face interactions were reported in the first of the articles in this series, and focused on the elucidation of adhesion problems in tablet compression. It was hypothesized that the intermolecular interactions between drug molecules and the punch face was the first step (or criterion) in the adhesion process, and that the rank order of adhesion during tablet compression should correspond with the rank order of these energies of interaction. That is, the interaction between the molecular structure of the drug and the metal surface determines the primary interaction event or relative potential for adhesion, while the mechanical processes and/or lubrication effects may subsequently impact the extent of adhesion. Molecular simulations and atomic force microscopy were used to establish the rank order of the work of adhesion of a series of profen compounds. The results predicted that the relative degree of drug substance-punch face adhesion should decrease in the order of ketoprofen > ibuprofen > flurbiprofen. In this study, the authors investigated whether the rank order of the work of adhesion established on the molecular level and interparticulate level holds true in the tableting environment by measuring tablet take-off force, ejection force, and visual observation of the punch surfaces for both pure drug compacts and formulated tablets. The compaction simulator was used for pure profen compacts, while the instrumented tablet press for formulated tablets. Due to the inability to extract the adhesion force component from the total ejection force measurement, tablet ejection force was not used as a criterion to judge the adhesion behavior of the model compounds. The criteria used for judgement of punch face adhesion were tablet take-off force and visual observation of the punch faces. The rank order of adhesion for both pure drug and formulated tablets was determined to follow the order of ketoprofen > ibuprofen > flurbiprofen. The effect of run time on adhesion behavior was also investigated. Therefore, the rank order of the punch-face adhesion tendencies for the series of profen compounds was determined, and found to agree with the data from the predictive methods reported in the first article.

Adhesiveness↗
PubMed1996

Characterization of compressibility and compactibility of poly(ethylene oxide) polymers for modified release application by compaction simulator.

Poly(ethylene oxide) polymers (PEO) appear to have great potential for controlled release applications. These polymers are hydrophilic with good water solubility, low toxicity, and high swelling capacity. As part of formulation optimization for a large-scale solid dosage form production, physicomechanical characterization of PEO was undertaken using a compaction simulator. Heckel plots for all PEOs were constructed, and yield pressures (Py) at different punch velocities were calculated from the linear portion of the plots. Low Py values, increase of Py with increasing punch speed, upward curvature of the plot, and strain rate sensitivity values indicate that the densification process and consolidation mechanism for PEOs of various molecular weights (0.2 x 10(6) to 7 x 10(6)) are identical and follow plastic deformation. PEOs have a high degree of crystallinity (57-85%) and show significant axial recovery (15-25%) upon decompression and ejection. The low Py values (58-78 MPa) and low mean compaction pressures demonstrate that volume reduction (compressibility) under pressure is excellent. However, due to viscoelastic behavior and large axial expansion, tablets of relatively low tensile strength are produced. These observations suggest the need to blend PEO with highly compactible excipients in order to produce tables on a high-speed production press.

Molecular Weight↗
PubMed1996

Compaction simulator studies of a new drug substance: effect of particle size and shape, and its binary mixtures with microcrystalline cellulose.

The compaction characteristics of a new drug substance with two crystal habits and particle size fractions as well as its binary mixtures with microcrystalline cellulose were studied using an integrated compaction research system under 300 and 450 MPa pressures. The results indicate that the drug substance has poor intrinsic compaction properties. The three-dimensional hexagonal crystal habit or smaller particle size consistently produced a slightly higher total work of compaction as compared with the cubic brick habit or larger particle size, respectively. However, neither crystal habit produced a coherent compact. The compactability of the drug substance was improved by the inclusion of microcrystalline cellulose, and the crushing strength of the compacts increased as the amount of microcrystalline cellulose in the binary mixture was increased. Such correlation was not observed when the compaction data were evaluated using either the Heckel equation or the percentage porosity change as a function of applied pressure.

Cellulose↗
PubMed1992

Effects of compaction and simulated root channels in the subsoil on root development, water uptake and growth of radiata pine.

Effects of subsoil compaction and simulated root channels (perforations) through the compacted layer on root growth, water uptake, foliar nutrient concentration and growth of radiata pine (Pinus radiata D. Don) were studied in a field experiment where a range of treatments were applied in reconstituted soil profiles. Subsoil compaction adversely affected root penetration in deeper parts of the soil and consequently caused greater water stress in trees. However, the effect of compaction was largely overcome when the subsoil was perforated to render 0.2% of the soil volume into vertical channels. Roots showed a remarkable ability to reach the points of low penetration strength and to travel through them to deeper parts of the profile. Perforations through compacted soil layers at a relatively low frequency may be a practical solution to allow root development into deeper parts of the soil and allow greater soil water exploration by roots.

Journal Article↗
PubMed2000

Thermodynamic analysis of compact formation; compaction, unloading, and ejection. I. Design and development of a compaction calorimeter and mechanical and thermal energy determinations of powder compaction.

The aim of this investigation was to determine and evaluate the thermodynamic properties, i.e. heat, work, and internal energy change, of the compaction process by developing a 'Compaction Calorimeter'. Compaction of common excipients and acetaminophen was performed by a double-ended, constant-strain tableting waveform utilizing an instrumented 'Compaction Simulator.' A constant-strain waveform provides a specific quantity of applied compaction work. A calorimeter, built around the dies, used a metal oxide thermistor to measure the temperature of the system. A resolution of 0.0001 degrees C with a sampling time of 5 s was used to monitor the temperature. An aluminum die within a plastic insulating die, in conjunction with fiberglass punches, comprised the calorimeter. Mechanical (work) and thermal (heat) calibrations of the elastic punch deformation were performed. An energy correction method was outlined to account for system heat effects and mechanical work of the punches. Compaction simulator transducers measured upper and lower punch forces and displacements. Measurements of the effective heat capacity of the samples were performed utilizing an electrical resistance heater. Specific heat capacities of the samples were determined by differential scanning calorimetry. The calibration techniques were utilized to determine heat, work, and the change in internal energies of powder compaction. Future publications will address the thermodynamic evaluation of the tablet sub-processes of unloading and ejection.

Calibration↗
PubMed1997

Influence of bone quality on the stress distribution. An in vitro experiment.

Adequate bone quality and stress distribution to the bone are of decisive importance for implant success. The purpose of this in vitro study was to investigate the influence of bone quality on the stress distribution using 2 implant-bone mimicking models, simulating compact and cancellous bone quality. The resin model was made of an acrylic resin only simulating compact bone quality. The hybrid model was made of 2 kinds of materials, acrylic resin covered with a 1-mm layer of urethane to simulate cancellous bone quality. An implant was embedded in each model, and the abutment and suprastructures were connected to the implant. A strain gauge was placed perpendicular to the implant on the surface of the model and a small accelerometer was attached to the abutment. When an impact load was applied to the suprastructure, both strain and acceleration were measured. Both abutment acceleration and surface strain in the hybrid model decreased rapidly as time progressed when compared to the resin model. Abutment accelerations in the resin model were significantly lower than those in the hybrid model. In the hybrid model, the strain increased as the loading site was moved closer to the strain gauge. The influence of loading sites on strain in the resin model was greater than in the hybrid model. Therefore, the occlusal stress was distributed more widely in the hybrid model than in the resin model. This may indicate that occlusal stress in compact bone may have a tendency to concentrate in particular regions.

Acrylic Resins↗
PubMed1999

Capsule filling machine simulation. I. Low-force powder compression physics relevant to plug formation.

The objective of this study was to simulate powder plug formation and explore the low-force powder compression physics of the process. A single-ended saw-tooth waveform was used to make powder plugs, representing no. 1 size capsules, at constant punch speeds of 1, 10, and 100 mm/sec on a tablet compaction simulator. Plugs of different heights (4, 8, and 12 mm) were made in a prelubricated die from three materials: Avicel PH 102, anhydrous lactose, and Starch 1500. The compression data were fit to Heckel's pressure-density relationship, Kawakita's pressure-volume relationship, and Shaxby-Evans's exponential relationship. Heckel analysis of this low-pressure range data revealed "apparent yield pressures" of 25-70 MPa, which were dependent upon the material type, machine speed, and plug height. Shaxby-Evans's relationship was found to hold in that the axial load transmission decreased exponentially with increased plug height/diameter ratio. A dramatic decrease in the coefficient of lubrication, R, with increase in plug height was attributed to poor axial load transmission through the length of the plug. Kawakita's pressure-volume relationship fit the plug formation data very well, and it was evident from this model (Kawakita constant, a) that Avicel PH 102 had the largest available volume for reduction. The plug formation process can be simulated using a programmable tablet compaction simulator. Overall, the data analysis demonstrated that the compression models available for tableting that were used in this study can also be applied to the powder plug formation process with appropriate interpretation.

Capsules↗
PubMed2000

The influence of varying precompaction and main compaction profile parameters on the mechanical strength of compacts.

The purpose of this work was to investigate how altering the method of force application could be beneficial to tablet production in order to increase tablet strength and eliminate or minimize the incidence of capping and lamination. An integrated compaction research system (i.e., compaction simulator) was used throughout this study. Compaction profiles containing a single compaction event and a double (pre- and main) compaction event were created. The ratio and magnitude of the pre- and main compaction pressures were varied and the time interval between the pre- and main compaction events was altered to determine the effects on the crushing strengths and capping tendency of the final compacts. In all cases, for a given pressure, the double compaction event produced stronger tablets than the single compaction event. When the ratio and magnitude of the pre- and main compaction pressures were varied, the results differed depending on the material undergoing compaction. Dicalcium phosphate/microcrystalline cellulose and pregelatinized starch tablets had no significant difference in crushing strength values regardless of whether the precompaction pressure was less than or greater than the main compaction pressure. However, both direct compression (DC) acetaminophen and DC ibuprofen were found to have increased crushing strengths and decreased capping/lamination when the precompaction pressure was less than the main compaction pressure. When the time interval between the pre- and main compaction events was varied from 30 to 500 msec, no significant difference in the crushing strength or capping/lamination tendency was observed. It was concluded that the effect of altering the ratio and magnitude of the pre- and main compaction pressures varied from one material to another, suggesting that the profiles should be tailored individually for the specific material undergoing compaction.

Tablets↗
PubMed2001

Thermodynamic analysis of compact formation; compaction, unloading, and ejection. II. Mechanical energy (work) and thermal energy (heat) determinations of compact unloading and ejection.

A compaction calorimeter, previously described (DeCrosta, M.T., Schwartz, J.B., Wigent, J.B., Marshall, K., 2000. Thermodynamic analysis of compact formation; compaction, unloading, and ejection. I. Design and development of a compaction calorimeter and mechanical and thermal energy determinations of powder compaction. Int. J. Pharm. 198, 113--134), was utilized to evaluate the thermodynamics of the unloading and ejection of compacts of Avicel pH102, Emcompress, Fast-Flo #316, Starch 1500, and acetaminophen (APAP). A constant strain waveform, applied by a compaction simulator, enabled the separate thermodynamic evaluation of unloading from compaction. The brittle materials, Fast-Flo #316 and Emcompress, displayed the most unloading work, and the plastic/self-lubricating materials, Avicel and Starch 1500, displayed the least. Unloading heat values were negative for all materials, except APAP. APAP's positive heat values indicated the breaking of bonds during unloading as a result of its highly elastic nature. Positive internal energy changes of unloading, which indicate the net breaking of bonds, were observed for APAP and Emcompress over the compaction forces tested. Negative energy changes for Starch 1500, Fast-Flo #316, and Avicel became positive with increasing compaction forces. Ejection work increased with increasing compaction force for the brittle materials, whereas smaller ejection work values for Avicel, Starch 1500, and APAP remained constant. Increasing negative heat values as a function of compaction force were observed for Fast-Flo #316 and Emcompress. Negative internal energy values for ejection were observed for Fast-Flo #316 and Emcompress, which indicates net bond formation as a result of high shear of the compact with the die wall. Internal energy changes for Starch 1500, Avicel, and APAP, were approximately zero, indicating the absence of net bonding or bond formation during the process.

Algorithms↗
PubMed2001

Dynamic solid-state and tableting properties of four theophylline forms.

Relationships between solid-state, densification and compact properties of theophylline monohydrate (TMO), a mixture of forms (TMIX), and anhydrous polymorphs I (TA-I) and II (TA-II) were evaluated. Solid-state identification of powders and compacts was accomplished by powder X-ray diffraction. A compaction simulator was used to assess deformation behaviour of the powders and to prepare compacts. Porosity and tensile strength of the compacts were determined after 1,24, and 168 h of storage at 22% relative humidity. TA-II was stable, whereas TA-I, TMIX and TMO partially transformed to the TA-II form during storage. All theophylline modifications primarily deformed by plastic flow. Increased water content decreased resistance towards densification and deformation of TMIX and TMO when compared to TA-II or TA-I, demonstrating viscoelasticity. Permanent densification behaviours of TMIX and TMO approached to that of TA-II during storage. Tensile strength of the different theophylline forms were practically equal after 1 h of storage. Tensile strength and porosity of TMIX and TMO compacts increased during the storage. Dynamic solid-state transformations from TMO, TMIX and TA-I to TA-II were associated with parallel changes in their densification and compact properties. The extent of these changes was also dependent on the materials' water content.

Bronchodilator Agents↗
PubMed2006

Compression physics in the formulation development of tablets.

The advantages of high-precision dosing, manufacturing efficiency, and patient compliance make tablets the most popular dosage forms. Compaction, an essential manufacturing step in the manufacture of tablets, includes compression (i.e., volume reduction and particle rearrangement), and consolidation (i.e., interparticulate bond formation). The success of the compaction process depends not only on the physico-technical properties of drugs and excipients, especially their deformation behavior, but also on the choice of instrument settings with respect to rate and magnitude of force transfer. This review discusses various properties of drugs and excipients, such as moisture content, particle size and distribution, polymorphism, amorphism, crystal habit, hydration state, and lubricant and binder level of the blend that have an influence on compaction. Tableting speed and pre/main compression force profile, also have a bearing on the quality of the final tablet. Mechanistic aspects of tableting can be studied using, instrumented punches/dies, instrumented tableting machines, and compaction simulators. These have potential application in pharmaceutical research and development, such as studying basic compaction mechanism, process variables, scale-up parameters, trouble shooting problem batches, creating compaction data bank, and fingerprinting of new active pharmaceutical ingredients (APIs) or excipients. Also, the mathematical equations used to describe compaction events have been covered. These equations describe density-pressure relationships that predict the pressures required for achieving an optimum density. This understanding has found active application in solving the analytical problems related to tableting such as capping, lamination, picking, sticking, etc. Mathematical models, force-time, force-distance, and die-wall force parameters of tableting are used to describe work of compaction, elasticity' plasticity, and time dependent deformation behavior of pharmaceuticals. Various indices of tableting performance such as the bonding index, brittle fracture index, and strain index can be used to predict compaction related problems. Compaction related physico-technical properties of commonly used tableting excipients have been reviewed with emphasis on selecting suitable combination to minimize tableting problems. Specialized tools such as co-processing of API and excipients can be used to improve their functionality.

Chemistry, Pharmaceutical↗
PubMed2003

Hollow filler-binders as excipients for direct compaction.

PURPOSE: As an effect of their plastic deformation behavior, ductile materials create a large surface for bonding during compaction. However, a serious drawback is their high lubricant sensitivity, preventing the formation of strong bonds. The purpose of this study was both an increase in compactibility and a reduction of the lubricant sensitivity of ductile filler-binders by using hollow particles. This was illustrated for inulin. METHODS: Both solid and hollow inulin particles were prepared by spray-drying. Unlubricated tablets and tablets containing 0.5% magnesium stearate were compressed in a compaction simulator, operating at 300 mm/s. The tablet crushing strength was determined with a Schleuniger apparatus. RESULTS: The compaction of unlubricated, solid inulin particles showed that the product had good compatibility. This was caused by plastic deformation of the ductile, amorphous material under load, creating a large surface for bonding. After lubrication, however, the bonding properties decreased significantly, which was caused by the presence of a lubricant film. Hollow inulin particles have an increased compactibility as compared with solid particles and a strongly reduced lubricant sensitivity. Scanning electron micrographs show that hollow particles fragment before they start plastic deformation. This fragmentation behavior is supported by tablet surface area measurements and calculation of the buckling strength. This effect was responsible for both a higher crushing strength and a lower lubricant sensitivity as compared with solid inulin particles. CONCLUSIONS: Compactibility of inulin particles can be increased, and lubricant sensitivity can be decreased by using hollow instead of solid particles.

Drug Compounding↗
PubMed2006

A study on the effect of wet granulation on microcrystalline cellulose particle structure and performance.

PURPOSE: The aim of this study was to investigate the mechanism of the effect of wet granulation process on the compaction properties of microcrystalline cellulose (MCC). METHODS: MCC alone and with hydroxypropyl cellulose (HPC) as a binder were wet granulated by a high-shear process using different granulation parameters (over- and undergranulated). Overgranulated batches were also ball milled after drying and compared to the unmilled material. MCC starting material and granulation were characterized for particle size distribution, surface area, porosity, and isothermal moisture uptake. Compaction behavior of the MCC and granulations was also studied using a compaction simulator. RESULTS: In all cases, the wet granulation process decreased MCC primary particle porosity. Wet granulation also reduced compactibility of MCC to different degrees. Overgranulated batch with HPC showed the lowest compactibility and was less compactible than the batch without HPC granulated using the same parameters. Ball-milled material showed an increase in porosity and was significantly more compactible than the unmilled granulation from the same batch. CONCLUSIONS: The decrease in MCC compactibility after granulation is associated with the decrease in MCC primary particle porosity and in some cases with the formation of large dense granules as well. Under certain conditions, milling seems to counteract the effect of wet granulation on MCC compactibility.

Adsorption↗
PubMed1997

A compact disc containing simulations of hearing impairment.

The author has produced a compact disc (CD) which contains a series of simulations of the effects of cochlear hearing loss. The following aspects are simulated: threshold elevation combined with loudness recruitment; reduced frequency selectivity; and threshold elevation, loudness recruitment and reduced frequency selectivity all together. The effects are demonstrated using speech in quiet and in a background of noise, and using a piece of music with a wide dynamic range. The CD also includes simulations of the effect of having a conventional 'linear' hearing aid, and of having aid incorporating dual-channel fast acting compression. Finally, the CD contains demonstrations of the 'occlusion effect' and the benefits of having a deeply fitting earmould or hearing aid. The purpose of this note is to describe some of the uses of the CD for teaching and educational purposes and to indicate which tracks will be most effective for specific purposes.

Auditory Threshold↗