Determination of precompression and compression force levels to minimize tablet friability using simplex

Abstract

Pilot simplex experiments for improving the tablet strength of three aspirin tablet formulations based on precompression and compression forces were presented. As each simplex moved towards the direction of the optimum, the friability was being minimized and the crushing strength was concomittantly being maximized. Because it followed a systematic direction, simplex process would locate a local optimum rapidly. The appropriate levels of precompression and compression forces that produced tablets with the desired strength were attained in five trials. By contrast, random search for this force combination required at least ten trials. Simplex technique is a cost and time effective means for determining the precompression and compression forces that will reduce the friability or increase the hardness of a tablet formulation. Results appeared to also indicate that crushing strength might be a more reliable measure of tablet strength than friability.     

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     

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.     

Optimization of Tablet Friability,Maximum Attainable Crushing Strength,Weight Variation and In Vitro Dissolution by Establishing In-Process Variable Controls

Abstract

The level of intragranular microcrystalline cellulose, volume of granulating water, granulation moisture content and tablet crushing strength were used as in-process variables for optimizing tablet friability, maximum attainable crushing strength, weight variation and in vitro dissolution. A computer optimized experimental design (COED) allowed optimal characterization of the variables by designing 22 experiments. The results were analyzed by means of a general quadratic response surface model. Response surfaces were generated for tablet friability, maximum attainable crushing strength, weight variation and in vitro dissolution as a function of the in-process variables. The study provided a useful method in setting optimum ranges for the in-process variables in order to optimize the important tablet parameters.     

Process Considerations in Reducing Tablet Friability and Their Effect on in vitro Dissolution

The tablet friability resulting from manufacturing process variations was studied for two differently sized tablets using the same formulation. Granulations containing lower moisture contents required higher compression and ejection forces to manufacture a tablet at a given hardness, although this did not influence friability. Increased tablet hardness (and to a lesser extent decreased tablet thickness) decreased the tablet friability of the larger tablet. An increase in the quantity of granulating fluid increased the granulation particle size and slightly improved compactibility without significantly affecting friability. Tablet dissolution increased as the quantity of granulating fluid was decreased. There was a strong interaction, with respect to dissolution, between moisture content and the amount of granulating fluid. Tablet hardness did not significantly influence dissolution. Doubling the quantity of magnesium stearate in the granulation in one tablet strength decreased the maximum tablet hardness that could be obtained, and for the other tablet strength increased friability. It also resulted in slower tablet dissolution.     

The Effect of Lubricants on the Properties of Chloroquine Phosphate Tablets

Abstract

The properties of tablets prepared from different size fractions of chloroquine phosphate granules using different lubricants were evaluated. Lubricants used were magnesium stearate, stearic acid and talc, tablet properties studied include weight variation, crushing strength, friability and disintegration time

The effects obtained were largely dependent on the type and concentration of lubricant. Generally, as granule size increased, tablets were found to show increased weight variation, decreased hardness and increased friability. With tablets containing talc as lubricant, disintegration time was shown to decrease with increase in granule size.

There appears to be an optimum lubricant concentration for the compression of different granule size fractions.     

Physical Properties of Granules Containing Polysorbate 80

The friability and crushing load of granules containing polysorbate 80 were determined. It was found that while polysorbate 80 decreased granule hardness, as indicated by the load required to crush it, friability values increased to a maximum then decreasing at higher polysorbate 80 concentration. Thus the use of granule friability to measure granule strength may be erroneous unless good correlation between granule friability and direct crushing weight was obtained.

Direct measurement of granule strength tends to vary with granule shape and size giving a rather wide scatter of results. For overcoming this difficulty, tablet triturates could be prepared and the crushing strength determined. The crushing strength of the tablet triturates was found to be similar to that of granules but with a smaller scatter and more easily handled.

Studies of other physical properties of the granules containing polysorbate 80 were also made. Small amounts of the nonionic surfactant (0.002 - 0.2%) generally improved granule fluidity as characterised by the orifice flow velocity and the angle of repose of the granules.     

Physical Properties of Granules Containing Polysorbate 80

Abstract

The friability and crushing load of granules containing polysorbate 80 were determined. It was found that while polysorbate 80 decreased granule hardness, as indicated by the load required to crush it, friability values increased to a maximum then decreasing at higher polysorbate 80 concentration. Thus the use of granule friability to measure granule strength may be erroneous unless good correlation between granule friability and direct crushing weight was obtained.

Direct measurement of granule strength tends to vary with granule shape and size giving a rather wide scatter of results. For overcoming this difficulty, tablet triturates could be prepared and the crushing strength determined. The crushing strength of the tablet triturates was found to be similar to that of granules but with a smaller scatter and more easily handled.

Studies of other physical properties of the granules containing polysorbate 80 were also made. Small amounts of the nonionic surfactant (0.002 - 0.2%) generally improved granule fluidity as characterised by the orifice flow velocity and the angle of repose of the granules.     

The effect of precompression in a rotary machine on tablet strength

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.     

Effect of Crospovidone on the Physical Properties of Acetaminophen Tablets

Acetaminophen tablets containing minimum amount of excipients and varying amounts of cross linked polyvinyl pyrrolidone were prepared under accurately controlled conditions of compression speed and pressure. The disintegration time, dissolution rate, crushing force, friability as well as effect of temperature and humidity on these parameters during storage were determined. Increasing proportions of the cross linked polymer (1-10%) did not influence crushing force or friability but significantly decreased disintegration and dissolution time. Satishctory tablets with desired properties were obtained by incorporation of optimum quantity of crospovidone. Storage of acetaminophen tablets at room temperature and humidity for a period of 4 weeks did not alter any of the physical properties tested weekly. However the combined effect of elevated temperature and humidity on tablet properties, especially on the dissolution time was significant. The influence of incorporation of equal amounts of crospovidone intragranularly and intra-plus extragranularly on the properties of granules and tablets were also evaluated with scaled-up formulations.     

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.     

Effect of Crospovidone on the Physical Properties of Acetaminophen Tablets

Abstract

Acetaminophen tablets containing minimum amount of excipients and varying amounts of cross linked polyvinyl pyrrolidone were prepared under accurately controlled conditions of compression speed and pressure. The disintegration time, dissolution rate, crushing force, friability as well as effect of temperature and humidity on these parameters during storage were determined. Increasing proportions of the cross linked polymer (1-10%) did not influence crushing force or friability but significantly decreased disintegration and dissolution time. Satishctory tablets with desired properties were obtained by incorporation of optimum quantity of crospovidone. Storage of acetaminophen tablets at room temperature and humidity for a period of 4 weeks did not alter any of the physical properties tested weekly. However the combined effect of elevated temperature and humidity on tablet properties, especially on the dissolution time was significant. The influence of incorporation of equal amounts of crospovidone intragranularly and intra-plus extragranularly on the properties of granules and tablets were also evaluated with scaled-up formulations.     

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.     

Evaluation of Era-Tab as a Direct Compression Excipient

The physical and compressional properties of a modified rice starch, Era-Tab, were evaluated and compared with those of 4 commercially available direct compression excipients, namely, microcrystalline cellulose (Avicel PH-101), partially pregelatinized starch, spray-dried lactose (Super-Tab Lactose), and granular dicalcium phosphate dihydrate (Emcompress). It was found that Era-Tab possessed high flowability and adequate compressibility. The compacted material made with Era-Tab has a higher crushing strength and a lower friability than 3 other direct compression excipients, except microcrystalline cellulose. Tablets containing terfenadine of the same degree of hardness (10 kg) were also prepared using different direct compression excipients. The disintegration time of the tablets made with Era-Tab was approximately 2.5 min. The maximum of the accumulated percentage of terfenadine released from the tablet reached 90%, and 63.2% of it was released within 20 min. Both the powder characteristics and tablet properties show that the modified rice starch, Era-Tab, is a useful product as a direct compression tablet excipient.     

Moisture-Activated dry Granulation in a high Shear Mixer

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.     

Relationships between flow properties, compression behaviour and mechanical characteristics of prednisone-microcrystalline cellulose tablets

This paper describes the effects on the flow properties, as well as the changes in the compression behaviour, of microcrystalline cellulose (Avicel PH 101) incorporated with prednisone together with the mechanical properties of compacts made by direct compression from mixtures of these components.

There is a gradual degradation of the flow properties of the mixtures with increase proportions of prednisone. At the same time there is a close correlation between the parameters chosen to characterise the flow properties of the mixtures (unconfined yield stress, major consolidation stress and flow factor) and the compression work which influence the mechanical properties (crushing strength and friability) of compacts manufactured at low uniaxial compression forces.     

Optimization of Disintegration Time and Crushing Strength of a Tablet Formulation

Abstract

In an experiment with a factorial design, the following aspects were scrutinized: the impact on disintegration time and crushing strength caused by the loss-on-drying of the granulation; the granule-size distribution; the lubricant concentration; the compression force; and the pre-compression. Both with regard to disintegration time and crushing strength, these factors were found to have a significant influence: the loss-on-drying of the granulation; the fraction less than 0.150 mm; the concentration of magnesium stearate; and the compression force. A reduction of the tablet disintegration time was obtained by means of an increase of the granulation moisture; by an increase of the fine fraction; or by a reduction of the lubricant concentration or the compression force. The tablet crushing strength was increased by reducing the deviation of the granulation loss-on-drying from approximately 4.6 %; by a reduction of the fine fraction; by decreasing the lubricant concentration; or by increasing the compression force. The fraction larger than 0.300 mm had no significant influence; nor did the pre-compression. Further, there were no significant interactions.

By means of superimposing contour plots of disintegration time and crushing strength, a region was obtained where the requirements of disintegration time and crushing strength could be satisfied by controlling the processing variables.     

Optimization of Crushing Strength and Disintegration Time of a High-Dose Plant Extract Tablet by Neural Networks

Optimization of crushing strength and disintegration time of a high-dose plant extract tablet was reached after extensive experimentation. Effects of the processing parameters, like compression force and tooling, and also of the excipients were found to be significant. Best results for both disintegration time and crushing strength were obtained with a plant extract that was granulated by roller compaction before compression. To gain more information about the different effects, artificial neural networks (ANNs) and a conventional multivariate method (partial least squares [PLS]) were used for data analysis. The topologies of the neural networks of the feed-forward type were optimized manually and by pruning methods. All methods were tested for contemplated parameters, crushing strength, and disintegration time. In general, ANNs were found to be more successful in characterizing the effects that influence crushing strength and disintegration time than the conventional multivariate methods.     

Optimization of Disintegration Time and Crushing Strength of a Tablet Formulation

In an experiment with a factorial design, the following aspects were scrutinized: the impact on disintegration time and crushing strength caused by the loss-on-drying of the granulation; the granule-size distribution; the lubricant concentration; the compression force; and the pre-compression. Both with regard to disintegration time and crushing strength, these factors were found to have a significant influence: the loss-on-drying of the granulation; the fraction less than 0.150 mm; the concentration of magnesium stearate; and the compression force. A reduction of the tablet disintegration time was obtained by means of an increase of the granulation moisture; by an increase of the fine fraction; or by a reduction of the lubricant concentration or the compression force. The tablet crushing strength was increased by reducing the deviation of the granulation loss-on-drying from approximately 4.6 %; by a reduction of the fine fraction; by decreasing the lubricant concentration; or by increasing the compression force. The fraction larger than 0.300 mm had no significant influence; nor did the pre-compression. Further, there were no significant interactions.

By means of superimposing contour plots of disintegration time and crushing strength, a region was obtained where the requirements of disintegration time and crushing strength could be satisfied by controlling the processing variables.     

Optimization of Crushing Strength and Disintegration Time of a High-Dose Plant Extract Tablet by Neural Networks

Optimization of crushing strength and disintegration time of a high-dose plant extract tablet was reached after extensive experimentation. Effects of the processing parameters, like compression force and tooling, and also of the excipients were found to be significant. Best results for both disintegration time and crushing strength were obtained with a plant extract that was granulated by roller compaction before compression. To gain more information about the different effects, artificial neural networks (ANNs) and a conventional multivariate method (partial least squares [PLS]) were used for data analysis. The topologies of the neural networks of the feed-forward type were optimized manually and by pruning methods. All methods were tested for contemplated parameters, crushing strength, and disintegration time. In general, ANNs were found to be more successful in characterizing the effects that influence crushing strength and disintegration time than the conventional multivariate methods.