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

Using 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 problems.     

Determination of a Relationship Between Force-Displacement and Force-Time Compression Curves

A series of experiments were conducted to evaluate and compare force-displacement and force-time compression curves. A Stokes B-2 sixteen station rotary tablet press was instrumented with piezoelectric transducers to monitor compression and ejection forces (in addition to punch proximity) and interfaced with a microcomputer. Processing and material variables were examined for their effects on the direct parameters (ie. height and area) and derived parameters (ie. area:height ratio and maximum s1ope:height ratio) of the force-time compression curve. Upper punch displacement was estimated and force-displacement curves were plotted. The force-time curve was then divided into three segments pertaining to the three stages of upper punch movement: compression, relaxation, and decompression. The “relaxation” stage was defined as the portion of the compression force-time curve corresponding to the interval when the upper punch displacement was held constant. The total, net and elastic works of compaction were calculated and their relationships with the areas of the individual phases of the force-time compression curve were examined. It appears that the area under the cornpression force-time curve can be related satisfactorily to the work of compaction.     

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.     

Comparison of Methods for Evaluation of Friction During Tableting

Abstract

The friction between a tablet and the die wall can be evaluated by comparison of the forces on the upper and lower punches, i.e. force ratio (R-value) or force difference (FD, or by measuring the forces on the lower punch immediately before ejection (REF) or during ejection (EJF). These parameters were compared for different materials using an instrumented single-punch press. The compaction load and the dimensions of the compact had an obvious influence on all parameters studied. By correcting for differences in contact area between tablet and the die wall it appears possible to eliminate the influence on FD, REF and EJF from variation in tablet height. Several compaction loads within the range of interest have to be studied to get a complete picture of the behaviour of a tablet granulate. The different parameters did not always give correlating results and EJF appears to give the best prediction of adhesion problems.     

Comparison of Methods for Evaluation of Friction During Tableting

The friction between a tablet and the die wall can be evaluated by comparison of the forces on the upper and lower punches, i.e. force ratio (R-value) or force difference (FD, or by measuring the forces on the lower punch immediately before ejection (REF) or during ejection (EJF). These parameters were compared for different materials using an instrumented single-punch press. The compaction load and the dimensions of the compact had an obvious influence on all parameters studied. By correcting for differences in contact area between tablet and the die wall it appears possible to eliminate the influence on FD, REF and EJF from variation in tablet height. Several compaction loads within the range of interest have to be studied to get a complete picture of the behaviour of a tablet granulate. The different parameters did not always give correlating results and EJF appears to give the best prediction of adhesion problems.     

Adhesion of Tablets in a Rotary Tablet Press II. Effects of Blending Time,Running Time,and Lubricant Concentration

Abstract

Of the three essential functions of tablet lubricants, only the true lubricant and glidant properties have been studied in detail by objective means. Only recently has instrumentation which permits the objective measurement of the antiadhesion activity in a rotary tablet press been developed. Using a rotary press instrumented to measure the adhesion of tablets to the lower punch face, this study focuses on the adhesion of tablets in two direct compression systems. At any given compression force, adhesion of microcrystalline cellulose tablets lubricated with magnesium stearate appeared to decrease with increases in blending time or intensity of blending. Over a three-hour running time, adhesion force was found to increase to peak values and then to decline with both microcrystalline cellulose and hydrous lactose lubricated with magnesium stearate. However, ejection forces decreased gradually to apparently limiting values in each case. The adhesion of tablets to the lower punch face appeared to be affected partly by the condition of the tablet - die wall interface. Studies comparing lubricated and unlubricated microcrystalline cellulose suggest two opposing effects on tablet adhesion: (1) enhancing adhesion due to an increased reaction at the lower punch resulting from reduced die wall friction; and, (2) reducing the adhesion of tablets via the “antiadherent” effect. At the lubricant levels studied, stearic acid generally appeared to be less efficient than magnesium stearate in reducing both the adhesion and ejection forces in microcrystalline cellulose blends. However, with hydrous lactose blends, the true lubricant and antiadherent activities of stearic acid appeared to be greater than those of magnesium stearate at the 1.00% level of addition.     

A New Method to Evaluate the Elastic Behavior of Tablets During Compression

A new method to evaluate elastic/plastic behavior of tablets from tablet compression force-time data is presented. Tablets were compressed in an instrumented eccentric single-punch tablet machine. Equations for the calculation of relative elasticity were derived for both upper and lower punch forces. The experimental work was based on a 3² design having binder solution amount and atomizing air pressure as independent variables. Multilinear stepwise regression analysis was applied in studying the effects of granulation variables. It was concluded that the relative elasticity of tablets is dependent on binder solution amount. Furthermore, this study showed that the relative elasticity parameters can be useful in quantification of elastic behavior of tablets     

Development of Agglomerated Talc. III. Comparisons of the Physical Properties of the Agglomerated Talc Prepared by Three Different Processing Methods

Abstract

Agglomerated talc was prepared by the wet granulation method using a fluidized-bed granulator, a planetary mixer, and a high-speed, high-shear mixer. It was found that agglomerated talc produced by a fluidized-bed granulator is more porous, has a more irregular shape, has a lower bulk density, and has more binder-talc contacts. This higher surface area of binder-talc interface and the highly porous and irregular shape of the agglomerated talc produced by the fluidized- bed granulator result in stronger intergranular bonding. The resultant compact was harder. The compression force-time curve also showed that the time required to increase the upper punch force from 10% to 90% was greater for the compaction of the fluidized-bed granulated talc. The longer exposure to shear forces would enhance plastic flow and facilitate the formation of stronger bonds. Phenylpropanolamine HCl tablets containing 77.5 % agglomerated talc as the diluent were prepared. The properties of the tablet were found to be satisfactory. The agglomerated talc developed may be a promising direct compression diluent.     

Characterization of excipient and tableting factors that influence folic acid dissolution, friability, and breaking strength of oil- and water-soluble multivitamin with minerals tablets

The goal of this study is to characterize the formulation and processing factors that influence folic acid dissolution from oil- and water-soluble multivitamin with minerals tablet formulations for direct compression. The following parameters were studied: bulk filler solubility, soluble to insoluble bulk filler ratio, triturating agent (preblending carrier) solubility, disintegrant usage, compression pressure, and folic acid particle size. Folic acid particle size was determined by using light microscopy, and surface area was measured by using BET adsorption. The tablets were compressed on an instrumented Stokes B2 tablet press, and the friability, weight variation, and dissolution were measured according to USP methods, along with tablet breaking strength. In summary, we found the following factors to be critical to folic acid dissolution: bulk filler solubility (soluble fillers, such as maltose, increase folic acid dissolution); disintegrant amount (levels less than 0.4% (w/w) are ineffectual, whereas levels greater than 1.2% (w/w) did not further increase dissolution); and compression force (generally, maltose produce harder tablets). In addition, folic acid dissolution was less affected by changes in compaction pressure when a “super” disintegrant and maltose, as a bulk filler, were used. It was determined that the trituration agent did not play a significant role in folic acid dissolution. In the range of parameters studied, statistical analysis found no significant interactions between the parameters studied, which means they act independently in an additive manner. The results also show that no one factor is completely responsible for dissolution failure. Thus, it is the combination of formulation factors and processing conditions that collectively add up to produce dissolution failure; however, the use of a disintegrant and a soluble filler such as maltose can make a formulation more robust to the inevitable changes that can occur during commercial production.     

Characterization and Performance of a New Direct Compression Excipient for Chewable Tablets: Xylitab®

Abstract

Xylitab® is a commercially available direct compression form of xylitol. Two grades of this material, Xylitab 200 and Xylitab 100, were evaluated for compaction, flow, lubrication requirements, and dilution potential. As expected, the products required lubrication for tableting, and a level of 0.5% magnesium stearate and 0.5% stearic acid was found to give the best performance. Compaction profiles were generated using both an instrumented single-punch press and a rotary tablet press. Tablets up to hardness values of 20 Kp were obtained on the single-punch press; the maximum hardness values on the rotary press was 11 Kp. Flow behavior on the tablet presses was excellent as shown by tablet weight uniformity data with less than 1% RSD values. Further evaluation by Heckel analysis showed that both products exhibit brittle and viscoelastic behavior, and undergo elastic recovery primarily in the die. To test dilution potential, powdered acetaminophen was selected as a severe test material. Under these conditions, 20% drug still produced an acceptable tablet, but hardness values were reduced as expected. With a directly compressible grade of acetaminophen, a complete chewable formulation was successfully produced using Xylitab 200 as the main direct compression excipient and sweetening agent. Xylitab exhibits acceptable properties as a direct compression chewable tablet excipient and warrants further study.     

Moisture-Activated dry Granulation in a high Shear Mixer

Abstract

The applicability of a 25 litre high shear mixer for moisture-activated dry granulation was examined. Microcrystalline cellulose, potato starch or a mixture of 50% m/m of each was used as moisture absorbing material. The effects of water content, wet massing time, moisture absorbing material and dry mixing time on the size distribution, and the compressibility of the granulations were investigated. Tablets were compressed on a single punch press from all the granulations and on a rotary press from a few of the granulations.

It was shown that the physical properties of the tablets were primarily affected by the water content, the moisture absorbing material, and the compression force. Tablets with low mass variation, high crushing strength, low friability, and short disintegration time were achieved with both tablet presses by using a mixture of microcrystalline cellulose and potato starch as moisture absorbing material.     

The effect of precompression in a rotary machine on tablet strength

Abstract

The effects of precompression on tablet strength/main compression pressure profiles have been studied with an instrumented rotary tabletting machine. The advantages of precompression are dependent upon individual formulation components and their behaviour under stress, tablet shape, and machine speed. Model systems and the mechanisms by which precompression may improve tablet strength, are discussed.     

Instrumented and Computer Interfaced Single Punch Tablet Press for the Rapid Evaluation of Compression and Lubrication Behaviour

A low cost instrumented and computer interfaced single punch tablet press was developed for the rapid data aquisition of compression and lubrication properties of powders arid processed materials.

A Manesty type F3 tablet machine has been modified to enable the fitting of piezo electric load cells to both upper and lower punch assemblies. The paper describes how the modifications permit interchangability of a range of punch sizes and shapes and yet ensure good accuracy and reproducibility of compression end lubrication data.

The instrumentation is interfaced with a dedicated A. I. M. 65 microcomputer for the rapid conversion of the instrumentation outputs into compression force units and for statistical evaluation. The computer software also incorporates a novel method for the evaluation of lubrication properties from a single or a series of pre-determined compression events, using the some sensitivity for force measurement from the lower punch lord cell.

The compression data and the physical properties of the compacts can be stored and retreived as fingerprints using a P. E. T. microcomputer and a digital plotter. A date bank may then be developed for the evaluation of raw materials, product development, monitoring of production performance and trouble shooting.

The paper further describes the evaluation of new lubricants in comparison with magnesium stearate using the instrumentation described.     

New Parameters Derived from Tablet Compression Curves. Part I. Force-Time Curve

A great number of new parameters derived from tablet force-time curves are introduced. The crushing strength and friability of tablets were measured, and the dependence between the calculated compression parameters and the two tablet properties was studied. Tablets were made with an instrumented eccentric tablet machine using three direrent compression forces and three different compression speeds. The testing material was a-lactose monohydrate. This seems to be a limitation in this study, but our main purpose was to introduce these new compression parameters. The results showed that the suggested parameters described clearly different pattern of material behavior. We suggest that, especially together, these parameters may be used in the prediction of compression characteristics of different materials     

Adhesion of Tablets in a Rotary Tablet Press II. Effects of Blending Time, Running Time, and Lubricant Concentration

Of the three essential functions of tablet lubricants, only the true lubricant and glidant properties have been studied in detail by objective means. Only recently has instrumentation which permits the objective measurement of the antiadhesion activity in a rotary tablet press been developed. Using a rotary press instrumented to measure the adhesion of tablets to the lower punch face, this study focuses on the adhesion of tablets in two direct compression systems. At any given compression force, adhesion of microcrystalline cellulose tablets lubricated with magnesium stearate appeared to decrease with increases in blending time or intensity of blending. Over a three-hour running time, adhesion force was found to increase to peak values and then to decline with both microcrystalline cellulose and hydrous lactose lubricated with magnesium stearate. However, ejection forces decreased gradually to apparently limiting values in each case. The adhesion of tablets to the lower punch face appeared to be affected partly by the condition of the tablet - die wall interface. Studies comparing lubricated and unlubricated microcrystalline cellulose suggest two opposing effects on tablet adhesion: (1) enhancing adhesion due to an increased reaction at the lower punch resulting from reduced die wall friction; and, (2) reducing the adhesion of tablets via the “antiadherent” effect. At the lubricant levels studied, stearic acid generally appeared to be less efficient than magnesium stearate in reducing both the adhesion and ejection forces in microcrystalline cellulose blends. However, with hydrous lactose blends, the true lubricant and antiadherent activities of stearic acid appeared to be greater than those of magnesium stearate at the 1.00% level of addition.     

A Study of the Compactibility Characteristics of a Direct Compression and A Wet Granulated Formulation of Norfloxacin

Compaction characteristics of norfloxacin tablets manufactured by both wet granulation and direct compression procedures were studied with the aid of an instrumented single punch tablet press interfaced with a digital computer. Under comparable tabletting conditions, the direct compression formulation required less compressional force than the wet granulated formulation to produce tablets of similar breaking strengths, which indicates superior compactibility. The directly compressed tablets were found to disintegrate faster and release their active component more rapidly during the critical early stages of dissolu-tion. Dissolution and disintegration of the directly compressed tablets generally were less affected by changes in breaking strengths than those compressed from granulated systems.     

Instrumented and Computer Interfaced Single Punch Tablet Press for the Rapid Evaluation of Compression and Lubrication Behaviour

A low cost instrumented and computer interfaced single punch tablet press was developed for the rapid data aquisition of compression and lubrication properties of powders arid processed materials.

A Manesty type F3 tablet machine has been modified to enable the fitting of piezo electric load cells to both upper and lower punch assemblies. The paper describes how the modifications permit interchangability of a range of punch sizes and shapes and yet ensure good accuracy and reproducibility of compression end lubrication data.

The instrumentation is interfaced with a dedicated A. I. M. 65 microcomputer for the rapid conversion of the instrumentation outputs into compression force units and for statistical evaluation. The computer software also incorporates a novel method for the evaluation of lubrication properties from a single or a series of pre-determined compression events, using the some sensitivity for force measurement from the lower punch lord cell.

The compression data and the physical properties of the compacts can be stored and retreived as fingerprints using a P. E. T. microcomputer and a digital plotter. A date bank may then be developed for the evaluation of raw materials, product development, monitoring of production performance and trouble shooting.

The paper further describes the evaluation of new lubricants in comparison with magnesium stearate using the instrumentation described.     

Development of Agglomerated Talc. III. Comparisons of the Physical Properties of the Agglomerated Talc Prepared by Three Different Processing Methods

Agglomerated talc was prepared by the wet granulation method using a fluidized-bed granulator, a planetary mixer, and a high-speed, high-shear mixer. It was found that agglomerated talc produced by a fluidized-bed granulator is more porous, has a more irregular shape, has a lower bulk density, and has more binder-talc contacts. This higher surface area of binder-talc interface and the highly porous and irregular shape of the agglomerated talc produced by the fluidized- bed granulator result in stronger intergranular bonding. The resultant compact was harder. The compression force-time curve also showed that the time required to increase the upper punch force from 10% to 90% was greater for the compaction of the fluidized-bed granulated talc. The longer exposure to shear forces would enhance plastic flow and facilitate the formation of stronger bonds. Phenylpropanolamine HCl tablets containing 77.5 % agglomerated talc as the diluent were prepared. The properties of the tablet were found to be satisfactory. The agglomerated talc developed may be a promising direct compression diluent.     

The Evaluation of Fine-Particle Hydroxypropylcellulose as a Roller Compaction Binder in Pharmaceutical Applications

In solid dosage manufacturing, roller compaction technology plays an important role in providing cost control and a quality product. The objective of this study was to evaluate the effectiveness of fine-particle hydroxypropylcellulose (HPC) as a dry binder in roller compaction processing. The formula included acetaminophen (APAP), microcrystalline cellulose, fine-particle HPC, croscarmellose sodium, and magnesium stearate. The fine-particle HPC was incorporated into the formula at 4%, 6%, and 8% w/w levels. Three compaction pressures (30, 40, and 50 bars) were used for each formulation. The roller compaction equipment used in this study had a processing capacity of 40 to 80 kg/hr. A tablet compression profile was generated on a rotary tablet press, and compression forces used were 5, 10, 15, 20, and 25 kN. The significant criteria for tablet evaluation were capping, hardness, friability, ejection force, and drug dissolution. As the binder concentration of HPC increased, tablet capping decreased, and tablet friability improved. As the concentration of HPC increased, only slight differences were noted in tablet hardness. All the formulations pass the USP requirement of 80% APAP dissolved within 30 min. Using 8% HPC could eliminate the formula capping problem. The friability results were less than 1% at all compression forces. The minimum tablet ejection forces were found in the formulations prepared under 40 bars compaction pressure. The utility of fine-particle HPC as a roller compaction binder was established. The applicable binder concentrations and roller compaction pressures were found. Using HPC at these binder levels and operating parameters could overcome capping and friability problems and achieve the optimal tablet dosage forms.