Instrumented Tablet Press Research Articles

Downstream Processability of Crystal Habit-Modified Active Pharmaceutical Ingredient

Efficient downstream processing of active pharmaceutical ingredients (APIs) can depend strongly on their particulate properties, such as size and shape distributions. Especially in drug products with high API content, needle-like crystal habit of an API may show compromised flowability and tabletability, creating significant processability difficulties on a production scale. However, such a habit can be adapted to the needs of downstream processing. To this end, we modified the needle-like crystal habit of the model API 5-aminosalicylic acid (5-ASA). This study reports processability assessment of six representative crystal habits of 5-ASA (needles, plates, rectangular bars, rhombohedrals, elongated hexagons, and spheroids) in the context of direct compression using ring shear tester, flow rate analyzer, and instrumented tablet press. As expected, needles were very cohesive, had low flow rate (1.0 ± 0.08 mg/s), and low bulk density (0.14 ± 0.01 g/mL) but showed better tabletability, whereas the opposite w...

Preliminary study of an offline simultaneous determination of metoprolol tartrate and hydrochlorothiazide in powders and tablets by reflectance near-infrared spectroscopy

A preliminary study of the feasibility of using near-infrared spectroscopy (NIRS) for the offline simultaneous determination of metoprolol tartrate (MTP) and hydrochlorothiazide (HTZ) in powders and tablets has been carried out. An industrial tableting process was simulated using an instrumented tablet press replicator – Presster™. Conventional reference analytics were replaced with gravimetric analysis. The NIRS models for powder and tablet analysis were developed using 55 samples, and tested on 80 independent samples. Powder mixture components were weighed in glass vials to collect reference values, mixed and manually transferred to a tablet press replicator and compacted to form tablets. NIRS calibration models were developed using spectral and gravimetric reference data. The two model drugs were simultaneously quantified exhibiting root mean-squared error of prediction (RMSEP) of 1.69 and 1.31 mg for HTZ powder and tablet samples, respectively, and RMSEP of 3.15 and 3.00 mg for MTP powder and tablet samples, respectively. NIRS analysis of MTP and HTZ in powder and tablet form has not been reported elsewhere.

Compression parameters of hexagonal boron nitride on direct compression mixture of microcrystalline cellulose and modified starch

The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant “hexagonal boron nitride (HBN)” on direct compression powders. Lubricants such as magnesium stearate (MGST), glyceryl behenate, stearic acid, talc and polyethylene glycol6000 were studied and tablets were manufactured on a single station instrumented tablet press. This study comprised the continuation of our previous one, so mixture of microcrystalline cellulose and modified starch was used as a master formula to evaluate effects of lubricants on pharmaceutical excipients that undergo complete plastic deformation without any fragmentation under compression pressure. Bulk and tapped densities, and Carr’s index parameters were calculated for powders. Tensile strength, cohesion index, lower punch ejection force and lubricant effectiveness values were investigated for tablets. The deformation mechanisms of tablets were studied during compression from the Heckel plots with or without lubricant. MGST was found to be the most effective lubricant and HBN was found very close to it. HBN did not show a significant negative effect on the crushing strength and disintegration time of the tablets when we compared with MGST. Based on the Heckel plots at the level of 1%, formulation prepared with HBN showed the most pronounced plastic character.

Effect of repeated compaction of tablets on tablet properties and work of compaction using an instrumented laboratory tablet press

The repeated compaction of Avicel PH101, dicalcium phosphate dihydrate (DCP) powder, 50:50 DCP/Avicel PH101 and Starch 1500 was studied using an instrumented laboratory tablet press which measures upper punch force, punch displacement and ejection force and operates using a V-shaped compression profile. The measurement of work compaction was demonstrated, and the test materials were ranked in order of compaction behaviour Avicel PH101 > DCP/Avicel PH101 > Starch > DCP. The behaviour of the DCP/Avicel PH101 mixture was distinctly non-linear compared with the pure components. Repeated compaction and precompression had no effect on the tensile fracture strength of Avicel PH101 tablets, although small effects on friability and disintegration time were seen. Repeated compaction and precompression reduced the tensile strength and the increased disintegration time of the DCP tablets, but improved the strength and friability of Starch 1500 tablets. Based on the data reported, routine laboratory measurement of tablet work of compaction may have potential as a critical quality attribute of a powder blend for compression. The instrumented press was suitable for student use with minimal supervisor input.

Image Analysis Quantification of Sticking and Picking Events of Pharmaceutical Powders Compressed on a Rotary Tablet Press Simulator

The aim of this work was to develop a quantification method based on image analysis, able to characterize sticking during pharmaceutical tableting. Relationship between image analysis features and relevant mechanical parameters recorded on an instrumented tablet press simulator were investigated. Image analysis, based on gray levels co-occurrence matrices (GLCM), generated textural features of the tablet surface. The tableting simulator (Stylcam® 200R, Medelpharm), instrumented with force and displacement transducers, provided accurate records. The tablet defects and compaction process parameters were studied using three pharmaceutical powders (Fast-Flo® lactose, anhydrous Emcompress® and Avicel® PH200 microcrystalline cellulose), five compression pressures (60 to 250 MPa), five lubricating levels, and three types of punches (standard steel, amorphous hard carbon and anti-sticking punches). Texture parameters made it possible to quantify with precision tablets’ aspect. The selected parameter IC2 (Information on Correlation 2) plotted versus the ratio between the ejection shear stress (Esh) and the compression pressure (Cp) let appear a relevant knowledge space where it was possible to identify a normal and a degraded tableting mode. A positive link between those two parameters was shown. Since the Esh/Cp ratio was related to image analysis results, it proved to be an interesting defect tag.

Effects of some lubricants and evaluation of compression parameters on directly compressible powders

The objective of this study was to investigate the effects of conventional lubricants including a new candidate lubricant “Hexagonal boron nitride (HBN)” on direct compression powders. Lubricants such as magnesium stearate, glyceryl behenate, stearic acid, talc and polyethylene glycol6000 were studied in this article. Tablets were manufactured on an instrumented tablet press with various lubricant concentrations. Bulk and tapped densities, and Carr’s index parameters were calculated for powders. Tensile strength, cohesion index, lower punch ejection force and lubricant effectiveness values were investigated for tablets. The deformation mechanisms of tablets were studied during compression from the Heckel plots with or without lubricants. Powders formulated with MGST and HBN showed better flow properties based on Carr’s index. MGST was found to be the most effective lubricant based on lubricant effectiveness for tablets. HBN was found very close to MGST with the same concentrations. Other lubricants showed less effectiveness than that of MGST and HBN. It is observed that an increase in the concentration of HBN leads to decreased tensile strength and cohesion index values because of its surface-covering property. Despite covering property, HBN had no significant effect on disintegration time. Based on the Heckel plots at the level of 1%, HBN showed the most pronounced plastic character.

Relationship between crystal structure and mechanical properties of ranitidine hydrochloride polymorphs

Polymorphism plays a critical role during pharmaceutical development, as it helps in the selection of optimal solid form. In present study, mechanical properties of ranitidine hydrochloride polymorphs were studied using instrumented tablet press, to understand the effect of crystal packing on the compaction behaviour. Out-of-die compressibility plot and Heckel analysis confirmed greater plastic deformation of form II over form I. Detailed crystallographic examination revealed that form I has several weak C–H⋯O interactions across the ‘proposed slip plane’ parallel to (−2 0 2) that prevent slip under compaction pressure. On the other hand, crystal structure of form II was relatively more open and multiple slip were possible under compaction pressure. These crystallographic features offered increased compressibility and deformability to form II. In absence of an active slip plane system, closed crystal structure of form I resists deformation under compaction pressure and hence showed poor compressibility and higher mean yield pressure. However, form I showed greater tabletability at a given compaction pressure, by virtue of its greater bonding strength.

Compaction behavior and optimization of spray-dried lactose with various amorphous content

The purpose of this study was to investigate the influence of amorphous content in spray-dried lactose on tableting characteristics. To obtain different amorphous contents, spray-dried lactoses were prepared at various lactose concentrations in distilled water. Plain spray-dried lactose and hydrochlorothiazide-lactose based tablets were compressed on an instrumented tablet press. Heckel analysis indicated that relative density (D B ) and yield pressure (P y ) correlated with both the degree of crystallinity and particle size and shape. The compactibility of the tablets was found to increase with amorphous content up to 20 % and then decreased and leveled off as the amorphous content was greater than 30 %. At 30 % amorphous and higher the spray-dried lactose tablets exhibited dissolution and erosion rather than disintegration in distilled water which was observed with lower amorphous lactose. The results indicated that tablet disintegration was influenced by compaction pressure and amorphous level (p

Product of Modified Rice Starch (Era-Gel<sup>®</sup>) and its Utilization in Pharmaceutical Industry

Pregelatinized rice starch (Era-Gel ® ) was prepared by physical modification. The degree of pregelatinization was controlled to an appropriate level. With the addition of small amount of pregelatinized rice starch , a slightly sticky, damped mass was obtained. Pregelatinized rice starch was tested for a potential use as a tablet filler or binder in wet granulation process. Two hydrochlorothiazide formulations were compared. One formulation comprised HCTZ and PRS; the powder mixture was damped with water. The other formulation contained HCTZ, lactose as filter, corn starch as binder and also as tablet disintegrant. In the later case, the powder mixture was damped with starch paste. Both granulations were compressed on an instrumented tablet press. The tablets were evaluated for their hardness, friability, disintegration, and also dissolution. The results indicated that both formulations were comparable in all aspects. It dissolution was found to exceed the USP requirement. It was demonstrated that three components, i.e. , lactose, corn starch paste, and disintegrant could be replaced with only one single material, PRS. It was also found that PRS could perform well in acetaminophen tablet formulation which was a high-dose drug and tended to cap; however, small amount of extra binder and disintegrant were needed. It could be seen that PRS had a great potential use in wet granulation process.

Evaluation of Hexagonal Boron Nitride as a New Tablet Lubricant

In this study, hexagonal boron nitride (HBN) was evaluated as a new lubricant for pharmaceutical tablet manufacturing. The other conventional lubricants such as magnesium stearate (MGST), stearic acid (STAC), and glyceryl behenate (COMP) were also tested along with HBN. Tablets were manufactured on an instrumented single-station tablet press to monitor and quantify the lower punch ejection force (LPEF). The force ratio, tablet crushing strength, disintegration time, and thickness were measured. The lubricant film formation and lubricant distribution in tablets were studied using the scanning electron microscopy (SEM) and electron probe micro analyzer (EPMA). Based on the force ratio, a good lubrication was obtained at 1% for MGST and HBN; in contrast, STAC and COMP did not show a good lubrication. After 1%, all lubricants performed well. MGST was found to be the most effective lubricant based on LPEF–lubricant concentration profile. HBN provided a 50% decrease in LPEF at 2% lubricant concentration and was rated as an effective tablet lubricant. HBN was better than either STAC or COMP. Unlike MGST, HBN had no significant prolongation effect on tablet disintegration times.

Influence of Compacted Hydrophobic and Hydrophilic Colloidal Silicon Dioxide on Tableting Properties of Pharmaceutical Excipients

The effect of noncompacted and compacted hydrophilic as well as hydrophobic colloidal silicon dioxide (CSD) on tableting properties of three different pharmaceutical excipients used for direct compression, namely, Avicel® PH 101, Starch 1500®®, and Tablettose® 80, was investigated. Binary powder mixtures containing 0.5% CSD and 99.5% excipient were compressed on an instrumented single-punch tablet press, and the radial tensile strength/compaction load profiles were examined. The Ryshkewitch-Duckworth relationship shows that the influence of CSD on tablet strength was dependent on the hydrophobic and hydrophilic nature of the CSD and on the compaction characteristics of the excipients. Tablets from each excipient with and without CSDs were subjected to different levels of relative humidity at 20°C for 7 days. The sorption isotherms and the radial tensile strengths of the tablets after the storage period showed that neither hydrophilic nor hydrophobic CSD influenced the tablet properties of Avicel® PH 101, Starch 1500®®, and Tablettose® 80. Moreover, ternary powder mixtures containing magnesium stearate as a third component were compressed in order to study the influence of CSD on the deleterious effect of magnesium stearate on the interparticle bonding. The radial tensile strength/compaction load profiles and the residual and ejection forces of tablets made from ternary mixtures showed that CSD eliminated the negative effect of magnesium stearate on interparticle bonding while maintaining the lubrication action, in a manner that was affected by its hydrophobicity/hydrophilicity and by the particle deformation properties of the excipient upon compression.

Consolidation Behavior of an Experimental, Cross-Linked Polyalkyl Ammonium Polymer

The effect of various factors (i.e., particle size, lubricant, moisture, and excipients) on the tableting properties of DMP 504 powder, an experimental, cross-linked polyalkyl ammonium polymer, was studied using an instrumented single-punch tablet press. The results indicate that plastic deformation is the primary consolidation mechanism for DMP 504. Lubrication of DMP 504 with magnesium stearate resulted in negative interaction in compactibility. The increase in tablet hardness with increase in water content of DMP 504 (up to 2.5%) could be attributed to the lubricating effect of water. Increasing the water content above the optimum moisture range (i.e., 2.5% to 4.0%) caused a drastic reduction in tablet crushing strength due to the hydrodynamic resistance. A mixture of DMP 504 with microcrystalline cellulose or starch led to a positive interaction with respect to compactibility. A deviation in tablet strength from the linear interpolated value did not correspond to a deviation in tablet thickness. The improved compactibility for the mixture of DMP 504 and microcrystalline cellulose or starch is not related directly to the facilitated densification.

Compressional Characterization of Two Dextrose-Based Directly Compressible Excipients Using an Instrumented Tablet Press

The main objective of this work was to evaluate the compaction behavior and record the work and the force involved in the compaction of blends and granules of two dextrose-based directly compressed excipients using a single-punch instrumented tablet press. The second objective was to identify the predominant form of deformation for the two different directly compressible excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and/or Maltrin M 510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. All formulations were compressed at four different compressional forces and at a target tablet weight of 450 mg ± 5%. Results show that compacts prepared from Emdex using the direct compression method produced the lowest elastic work and die wall friction, and the best degree of lubrication. Wet granulation for Maltrin M 510 decreased elastic work, frictional work, and ejection force, and enhanced both net work and degree of lubrication. In general, wet granulation for both Emdex and Maltrin M 510 decreased the crushing strength of the tablets and enhanced the degree of lubrication, compared to direct compression formulations. All formulations showed similar shape pattern for plastic deformation, suggesting that the predominant mechanism of deformation is plastic deformation type a Heckel plots.

Prediction of physical properties of a novel polysaccharide controlled release system. I

TIMERx is a novel polysaccharide-based controlled release matrix technology. The matrix consists of the synergistically interacting polysaccharides xanthan gum and locust bean gum in the presence of a third component, often dextrose, and other tertiary components. The physical properties and compression characteristics of this system were studied using conventional characterisation equipment and by the assessment of the tensile strength of compacts produced on an instrumented tablet press. The granulation method had a profound influence on granule properties and compact strength. Dry mixing of the relevant components led to the production of weak compacts. Granulation in a fluid bed granulator produced hollow granules of low bulk density which produced relatively weak compacts. Only high speed mixer granulation produced tablets with the strength required for pharmaceutical processing. Subsequent studies indicated that the nature and concentration of secondary and tertiary components added to the granulation can further influence the nature of granules produced and tablets manufactured from them. The particle size of granules, and the distribution around the mean, also appear to be important. It is concluded that the physical properties of granules and tablet depend on a number of factors not easily delineated using conventional statistics.

Compressibility Characteristics of Matrices Prepared with Ethylcellulose Aqueous Dispersion

Granules of acetaminophen (APAP) and Lactose Fast Flo were prepared by wet granulation method using Surelease aqueous dispersion as a granulating liquid. Acetaminophen granules containing different total solids (from Surelease) were compacted into tablets using instrumented tablet press to investigate the effect of the levels of Surelease (total solids) on the compressional properties of various formulations. Measurements were made of their compressibility, force displacement, works and forces analysis during compaction. All formulations containing Surelease utilized the compaction energy better than formulations of the same composition prepared without Surelease. As the level of total solids from Surelease was increased in the formula, the compressibility characteristic was enhanced. Granules with Surelease exhibited better deformation and densification behaviors and gave tablets of better mechanical strength compared to control tablets.

Compressibility and compactibility properties of ethylcellulose

Compaction characteristics of various viscosity grades of ethylcellulose were examined using an instrumented tablet press. Four different data analysis techniques were employed to characterize the compactibility and compressibility data: tablet hardness-compression force profiles, ejected tablet Heckel analysis, work calculations from force-displacement data and force-time profile analysis. The calculated parameters derived from these approaches included the following: mean yield pressure from the Heckel analysis, net work and elastic work from the force-displacement data and the area to height ( A H ) ratio from force-time data. Lower viscosity grades of ethylcellulose were found to be more compactible as described by tablet hardness-compression force profiles. Lower viscosity grades also exhibited a lower mean yield pressure from the Heckel analysis, indicating greater compressibility. Higher viscosity grades exhibited a decrease in net work and an increase in elastic work. Higher viscosity grades also exhibited greater values for the A H ratio derived from force-time analysis, indicating lower compressibility. Higher viscosity grades of ethylcellulose showed increases in true density, melting point, and heat of fusion. The variation in compactibility and compressibility properties of different viscosity grades of ethylcellulose can be attributed to changes in the polymer's degree of order.

Influence of ionic strength on matrix integrity and drug release from hydroxypropyl cellulose compacts

Hydroxypropyl cellulose (HPC) is commonly used in formulating hydrophilic sustained release matrix tablets. Since ions can affect the degree of hydration and solution viscosity of HPC, there was concern whether these ionic changes will affect the drug release rate of tablets containing HPC. The objective of this study was to determine the effect of ionic strength solutions on the matrix integrity and drug release from HPC sustained release matrix compacts. In addition, the influence of HPC particle size and molecular weight on this system was investigated. Pure HPC and drug/HPC compacts were manufactured on an instrumented tablet press and tested for disintegration and dissolution under various ionic strength NaCl solutions. At ionic strengths less than 0.5, the compacts underwent swelling and gelation without any disruption of the matrix integrity or increased drug release. At 0.5–1.0 ionic strengths, certain types of HPC disaggregated and released drug rapidly. Above 1.0 ionic strengths, the compacts did not disaggregate, although release rates remained high for the high molecular weight HPCs. Fine particle size HPC was more resistant to the influences of ionic strength changes as was lower molecular weight HPC. The results of this study indicate that at normal physiological ionic strengths HPC compacts remain intact and release drug slowly.

Compression Behavior of Acetylsalicylic Acid Pellets

AbstractAn instrumented tablet press was used to study the compression behavior of different acetylsalicylic acid (AAS) formulations. Formulations of AAS crystals and uncoated AAS pellets have compression behavior similar to formulations of AAS pellets coated with acrylic resins (Eudragit RS) and mixed with a 20% of microcrystalline cellulose. Formulations of AAS coated pellets without any excipient exhibited a more plastic compression behavior then the other formulations. Matrix tablets of AAS were produced by compression of formulations of AAS coated pellets without any excipients.The drug release profile of the pellets before and after compression was also studied. Microcrystalline cellulose concentrations higher than 15% w/w were required to obtain tablets of coated pellets with drug release profiles similar to the coated pellets before compression. It can be concluded from the present work that compression data of coated particles can be useful to study the possible damage of the film coat of the par...

Instrumented Tablet Press Studies on the Effect of Some Formulation and Processing Variables on the Compaction Process

AbstractUsing an instrumented tablet press, compression force-time measurements were used to evaluate the effects of formulation and processing variables on the compaction process. The effects of tablet press speed, punch size, depth of upper punch penetration (into the die), and the setting of the overload spring mechanism were studied. The effects of tablet weight, particle size and amount of lubrication were also studied. Several direct compression materials which are believed to compact by different mechanisms were used in the study. The results indicate the sensitivity of the area under the compression force-time curve and the Area/Height ratio. Some of the changes seen in the area and A/H ratio were those which would be expected from a relatively simple model of compaction/compression. The results clearly show the usefulness of the instrumented tablet press as an analytical tool in the development of tablet formulations, the evaluation of processing requirements, and the remedy of tablet production ...

Crosslinked Starch as Sustained Release Agent

AbstractDifferent types of crosslinked starches and pregelatinized-crosslinked starches were evaluated for their use as hydrophilic matrices. Some fundamental properties of these chemically modified starches, e.g. granule swelling power and viscosity of the dispersion in function of pH and ionic strength, were studied. Dissolution tests and the rate and amount of water uptake were evaluated on tablets containing theophylline and modified starch (40/60 w/w), compressed on an instrumented tablet press at three different pressures (50,200 and 300 MPa.). Theophylline releasing profiles were determined using the paddle system at a rotational speed of 50 rpm Water, simulated gastric fluid, and simulated intestinal fluid were used as dissolution media. Crosslinked starches showed a poor swelling power and dispersion viscosity in comparison to pregelatinized starch and pregelatinized-crosslinked starches. The pregelatinized-crosslinked starches developed less swelling power than the pregelatinized starch, but the...