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.     

A study of the compaction process and the properties of tablets made of a new co-processed starch excipient

This article deals with the study of the energetic relationships during compaction and the properties of tablets produced from a co-processed excipient based on starch and called StarCap 1500?. This article compares it with the substance Starch1500?. The study also includes the mixtures of StarCap 1500? and the granulated directly compressible lactose Pharmatose DCL?15. The tablet properties tested included tensile strength and disintegration time, examined in dependence on compression force, and also a 0.4% addition of magnesium stearate. The results show a better compressibility of StarCap 1500 in comparison with Starch 1500 and a lower elastic component of energy. The tablets were stronger and disintegrated more rapidly, but the substance possessed a higher sensitivity to an addition of a lubricant than Starch 1500. Increasing portions of StarCap 1500 in the mixtures with Pharmatose DCL 15 increased the tensile strength of tablets, disintegration period as well as the sensitivity to an addition of a lubricant. From the energetic viewpoint, energy for friction was decreasing, while the energy accumulated by the tablet during compaction and the elastic component of energy were increased.     

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.     

Compaction Behaviour of Musol, A New Direct Compression Vehicle

The compaction characteristics of Musol, a new autocompressible vehicle derived through chemical modification of mucuna gum was investigated. Avicel PH 101, Zeparox and Encompress were used as reference tablet vehicles. Values of the mean yield stress derived from the analysis of Heckel plots indicate that Musol consolidates principally by plastic deformation, The effect of lubrication and recompression on friability, tensile strength and re-working potential of the tablets prepared with the vehicles were determined. While Avicel PH 101 yielded the strongest tablets, Musol showed the highest re-working potential for lubricated and un-lubricated slugs. On the basis of friability, tensile Values of strength and re-working potential, Musol than the grades of Zeparpx or Encompress performed better used in the study.     

Compaction Behaviour of Musol,A New Direct Compression Vehicle

Abstract

The compaction characteristics of Musol, a new autocompressible vehicle derived through chemical modification of mucuna gum was investigated. Avicel PH 101, Zeparox and Encompress were used as reference tablet vehicles. Values of the mean yield stress derived from the analysis of Heckel plots indicate that Musol consolidates principally by plastic deformation, The effect of lubrication and recompression on friability, tensile strength and re-working potential of the tablets prepared with the vehicles were determined. While Avicel PH 101 yielded the strongest tablets, Musol showed the highest re-working potential for lubricated and un-lubricated slugs. On the basis of friability, tensile Values of strength and re-working potential, Musol than the grades of Zeparpx or Encompress performed better used in the study.     

A study of the compaction process and the properties of tablets made of a new co-processed starch excipient

This article deals with the study of the energetic relationships during compaction and the properties of tablets produced from a co-processed excipient based on starch and called StarCap1500^®. This article compares it with the substance Starch1500^®. The study also includes the mixtures of StarCap 1500^® and the granulated directly compressible lactose Pharmatose DCL^®15. The tablet properties tested included tensile strength and disintegration time, examined in dependence on compression force, and also a 0.4% addition of magnesium stearate. The results show a better compressibility of StarCap 1500 in comparison with Starch 1500 and a lower elastic component of energy. The tablets were stronger and disintegrated more rapidly, but the substance possessed a higher sensitivity to an addition of a lubricant than Starch 1500. Increasing portions of StarCap 1500 in the mixtures with Pharmatose DCL 15 increased the tensile strength of tablets, disintegration period as well as the sensitivity to an addition of a lubricant. From the energetic viewpoint, energy for friction was decreasing, while the energy accumulated by the tablet during compaction and the elastic component of energy were increased.     

Comparative evaluation of soy polysaccharide as direct compression excipient

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

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

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.     

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.     

Comparative evaluation of soy polysaccharide as direct compression excipient

Abstract

Commercial soy polysaccharide (Emcosoy^R) has been evaluated as direct compression excipient in comparison with two frequently used materials, microcrystalline cellulose (Avicel pH 101) and pregelatinized maize starch (Sta-RX 1500).

Moisture sorption and desorption data analysed according to the Young and Nelson and the GAB equations and mechanical properties such as tensile strength, brittle fracture probensity, interparticle bonding isotropy and yield pressure of compacted excipients after storage at various environmental relative humidities are reported. Tableting characteristics such as punch force ratio, weight variation, tensile strength, friability, capping tendency, disintegration and dissolution of mixtures of the excipients and paracetamol are compared.

Emcosoy has been found to behave like Avicel as direct compression binder but like Sta-RX as disintegrant.     

Evaluation of Ludipress as a “Multipurpose Excipeent” for Direct Compression: Part I: Powder Characteristics and Tableting Properties

The powder characteristics and tableting properties of Ludipress, a lactose-based, free flowing granule containing povidone and crospovidone have been evaluated and compared to the physical blend of the base materials in Ludipress and to other filler/binders including Cellactose and Avicel PH 200.

The data were determined in order to evaluate flowability, bulk density, tapped density, Hausner ratio, angle of repose and particle size distribution. The particle morphology and constitution were examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was used to detect differences between lactose based products.

Several Ludipress samples exhibited a good batch-to-batch uniformity and flow characteristics compared to the physical blend and other excipients investigated.

The tableting parameters tested were crushing strength, friability and disintegration time. The ability to form coherent compacts was similar for Ludipress, Cellactose and Avicel PH 200, whereas tablets made from the physical blend resulted significantly softer. Determination of tablet disintegration time revealed a disintegration time minimum at about 100 MPa for Ludipress compacts. By augmenting compaction load from 100 to 185 MPa Cellactose showed an increase in disintegration time to more than 20 minutes. The disintegration times of Avicel PH 200 compacts were nearly constant and were also the shortest in the compaction load range examined.     

Evaluation of Ludipress as a “Multipurpose Excipeent” for Direct Compression: Part I: Powder Characteristics and Tableting Properties

The powder characteristics and tableting properties of Ludipress, a lactose-based, free flowing granule containing povidone and crospovidone have been evaluated and compared to the physical blend of the base materials in Ludipress and to other filler/binders including Cellactose and Avicel PH 200.

The data were determined in order to evaluate flowability, bulk density, tapped density, Hausner ratio, angle of repose and particle size distribution. The particle morphology and constitution were examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was used to detect differences between lactose based products.

Several Ludipress samples exhibited a good batch-to-batch uniformity and flow characteristics compared to the physical blend and other excipients investigated.

The tableting parameters tested were crushing strength, friability and disintegration time. The ability to form coherent compacts was similar for Ludipress, Cellactose and Avicel PH 200, whereas tablets made from the physical blend resulted significantly softer. Determination of tablet disintegration time revealed a disintegration time minimum at about 100 MPa for Ludipress compacts. By augmenting compaction load from 100 to 185 MPa Cellactose showed an increase in disintegration time to more than 20 minutes. The disintegration times of Avicel PH 200 compacts were nearly constant and were also the shortest in the compaction load range examined.     

Evaluation of surface and bulk characteristics of cellulose I powders in relation to compaction behavior and tablet properties

The particle properties and solid-state characteristics of two celluloses, Avicel PH101 and cellulose obtained from the alga Cladophora sp., were evaluated and related to the compaction behavior and the properties of the tablets made from them. The surface area of the celluloses was measured at different levels of penetration capacity, ranging from external surface area of particles to molecular texture with Blaine permeametry, Kr-gasadsorption, and solid-state NMR. The important cellulose fibril surface area was best reflected by solid-state NMR, although for the Cladophora cellulose, Kr-gas adsorption also resulted in a surface area of the order of what has been suggested earlier on the basis of the cellulose fibril dimensions. The difference in fibril dimension and, thereby, the fibril surface area of the two celluloses was shown to be the primary factor in determining their properties and behavior. Properties such as the crystallinity and the tablet disintegration could be related to the fibril dimensions. The Cladophora cellulose resulted in rather strong compacts that still disintegrated rapidly. The irregular surface morphology of the particles and the fragmenting behavior of Cladophora probably contributed to the strength of the tablets.     

Effects of tablet core dimensional instability on the generation of internal stresses within film coats part I: Influence of temperature changes during the film coating process

Abstract

Commercial-sized (10mm diameter and 3.1mm thick) flat-faced tablets, formed from three direct compression bases (Avicel PH101, Emcompress and Starch 1500) and from maize starch, were stored at ambient conditions for 1, 24, 48 and 72 hours following their compression, then exposed to temperatures of 30 and 40°C for two hours, and afterwards allowed to re-equilibrate to room temperature for another two hours. The aim of this was to simulate temperature variations experienced during a typical film coating process. During this time, dimensional changes of the tablets were measured by means of a free-armature transducer rig. The dimensional changes occurring during the preliminary ambient storage due to viscoelastic strain relaxation were found to be significant, but were much smaller In magnitude compared to those occurring during the subsequent heating/cooling cycle which is part of the tablet coating process. Tablets of Avicel, maize starch and Starch 1500 decreased in size during heating and expanded during cooling whereas tablets of Emcompress exhibited the opposite behaviour. The exposure temperatures were found to influence the magnitude of these strain changes. The results were evaluated in terms of subsequent relative humidity changes causing loss and gain of water from the tablets during this temperature cycle. Possible consequences of these dimensional changes relate to the creation of internal stress within the film coat which could result in coating defects (eg. cracking, edge splitting and bridging of intagliations).     

Effects of tablet core dimensional instability on the generation of internal stresses within film coats part I: Influence of temperature changes during the film coating process

Commercial-sized (10mm diameter and 3.1mm thick) flat-faced tablets, formed from three direct compression bases (Avicel PH101, Emcompress and Starch 1500) and from maize starch, were stored at ambient conditions for 1, 24, 48 and 72 hours following their compression, then exposed to temperatures of 30 and 40°C for two hours, and afterwards allowed to re-equilibrate to room temperature for another two hours. The aim of this was to simulate temperature variations experienced during a typical film coating process. During this time, dimensional changes of the tablets were measured by means of a free-armature transducer rig. The dimensional changes occurring during the preliminary ambient storage due to viscoelastic strain relaxation were found to be significant, but were much smaller In magnitude compared to those occurring during the subsequent heating/cooling cycle which is part of the tablet coating process. Tablets of Avicel, maize starch and Starch 1500 decreased in size during heating and expanded during cooling whereas tablets of Emcompress exhibited the opposite behaviour. The exposure temperatures were found to influence the magnitude of these strain changes. The results were evaluated in terms of subsequent relative humidity changes causing loss and gain of water from the tablets during this temperature cycle. Possible consequences of these dimensional changes relate to the creation of internal stress within the film coat which could result in coating defects (eg. cracking, edge splitting and bridging of intagliations).     

Investigation of the tableting behavior of Ibuprofen DC 85 W

The aim of the present study was to investigate the tableting behavior of Ibuprofen DC 85?W with special focus on the tablet disintegration time, the tablet crushing strength, and the sticking tendency to punch surfaces. To simulate production conditions, tableting was conducted on a rotary press, equipped with three compaction stations. An I-optimal design of experiments was used to analyze the influence of the pre-compaction, the intermediate compaction, and the main compaction force on the two responses: tablet disintegration time and crushing strength. It was shown that Ibuprofen DC 85?W showed a good tableting behavior with regard to both responses. The tablet disintegration was considerably affected by the maximum compaction force applied, but was also slightly affected by preceding compaction events. The tablet crushing strength was mainly affected by the maximum applied compaction force independent of the order of these forces. The sticking tendency of Ibuprofen DC 85?W was compared with that two other ibuprofen powder formulations in long-term tableting runs. Compared to the other two formulations, sticking was considerably lower with Ibuprofen DC 85?W. The sticking tendency was not influenced by the addition of an intermediate compaction force, but was remarkably reduced by the choice of the punch tip coating.     

Surrogate functionality of celluloses as tablet excipients

Background: The variety of excipients from different sources and prices to which we have access gives rise to the necessity to evaluate their functional characteristics. The aim of this work is to determine some physical and technological characteristics of celluloses from different sources, India and United States, to ascertain their functionality as tablet excipients. Methods: The used surrogate functionality properties are particle morphology and particle size distribution, compactibility, ejection pressure, and the disintegration properties of pure excipients and their compressed tablets. Results: The innovators Avicel and Croscarmellose show advantages over the generic celluloses Alfacel and Carmacel. Avicel PH 101 and 102 show an average of 26% greater compactibility than both types of Alfacel, whereas the compactibility of Croscarmellose is greater than that of Carmacel in about 50%. Avicel tablets compacted at a compaction pressure of 47 MPa exhibit shorter disintegration times (3.7 minutes) than Alfacel tablets (28 minutes), whereas Carmacel show better disintegrant properties than Croscarmellose. This occurs regardless of the similar particle morphology, size, and size distribution. As expected, all celluloses show low ejection pressures. Conclusion: The surrogate functionality properties of the generic celluloses are still considered as satisfactory to be used as tablet excipients, although they are inferior in some aspects to innovator celluloses. Alfacel and Carmacel have the potential to be used as filler, binder, and disintegrant, in the design of tablets. Moreover, one should bear in mind that the differences reported here may be altered because of a possible inter-batch variability and variations in the moisture content.     

Application of a novel automatic disintegration apparatus for the development and evaluation of a direct compression rapidly disintegrating tablet

An automatic disintegration tester was developed and used to explore disintegration mechanism and times of rapidly disintegrating tablets. DT50, the time required for a tablet to decrease in its thickness by half, allowed an unbiased determination of disintegration time. Calcium silicate concentration, Explotab? concentration, DiPac?/Xylitab? ratio as fillers, and compression pressure were evaluated using a central composite model design analysis for their DT50, tensile strength, and friability. Tablets that could reasonably be handled (friability <10%) could be produced. The expansion coefficient (n) and the exponential rate constant (k) for disintegrating tablets, originally measured by Caramella et al. using force kinetics, could be determined from axial displacement data measured directly without the need to assume that disintegration force generation was indicative of changes in tablet volume. The n values of tablets containing calcium silicate, Ditab? and/or Xylitab?, magnesium stearate, and Explotab? suggested that the amount of Explotab? was not a significant factor in determining the disintegration mechanism; however, the type of disintegrant used did alter the n value. Primojel? and Explotab?, which are in the same class of disintegrants, exhibited similar DT50, n, and k. Polyplasdone? XL exhibited a much higher n, while yielding faster DT50, suggesting that its performance is more dependent on facilitating the interfacial separation of particles. AcDiSol? showed no apparent moisture sensitivity in regards to disintegration efficiency. The use of the novel apparatus proved to be useful in measuring disintegration efficiency of rapidly disintegrating tablets and in providing valuable information on the disintegration phenomena.     

The effect of wax on compaction of microcrystalline cellulose beads made by extrusion and spheronization

The effect of wax on the deformation behavior and compression characteristics of microcrystalline cellulose (Avicel PH-101) and acetaminophen (APAP) beads is described. Beads of Avicel PH-101 and APAP formulations were prepared using extrusion and spheronization technology. A waxy material, glyceryl behenate, N.F. (Compritol), was added to the formulations in amounts ranging from 10% to 70% of total solid weight. Beads with a selected particle size range of 16-30 mesh were compressed with an instrumented single punch Manesty F press utilizing a 7/16-in. flat-faced tooling set. Compaction profiles were generated for the tablets to evaluate the effect of wax on the densification of beads containing wax. Beads made without wax (the control formulation) required greater compression forces to form cohesive tablets. As the amount of wax in the bead formulation was increased, the beads become more plastic and compressible. The Heckel equation which relates densification to compression pressure was used to evaluate the deformation mechanisms of the bead formulations. The analysis shows that as the level of wax in the bead formulation is increased, the yield pressure decreases, indicating that the beads densify by a plastic deformation mechanism.     

Comparison of Disintegrant and Binder Activity of Three Corn Starch Products

Abstract

This study demonstrates the differences obtained when using different corn starch products as both binder and disintegrant in pharmaceutical tablets. Formulations made with Fluftex W, Tablet White and Purity 21 starches were compared. In addition, Avicel PH101 was used in this study as a benchmark component whose properties are well understood.

Four test formulations containing hydrochlorothiazide were prepared by wet granulation. Starch was incorporated in both powder and paste form. All granulations were found to possess similar traits when evaluated based upon geometric mean diameter, particle size distribution, bulk/tap densities, powder flow rate and surface characteristics.

Tablets prepared from these granulations were shown to be similar when evaluated for degree of friability, weight and content uniformity. All starch formulations disintegrated within 30 seconds and produced similar dissolution profiles. Tablets produced with Avicel, however, were found to exhibit significantly longer disintegration times than the starch formulations. In addition, these tablets displayed a dissolution profile than was significantly different than the starch formulations, particularly during the earlier stages of the dissolution process.

When monitoring compression and ejection forces required to produce tablets of the same degree of hardness (≈6kg), Fluftex W and Tablet White granulations were found to use significantly lower forces than the Purity 21 granulation. This may be indicative of Fluftex W and Tablet White's superiority over Purity 21 in terms of binder capacity.