A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

A Comparative Evaluation of Some Starches as Disintegrants for Double Compressed Tablets

Abstract

The effect of different types and concentrations of some starches as disintegrants on the properties of aspirin tablets as a model for double compressed tablets was studied. The formulated tablets were evaluated using the U.S.P. official tests and some other selected nonofficial tests. These tests include: uniformity of weight, uniformity of content, disintegration, dissolution, hardness, friability and thickness. Maize starch was found to be the most suitable disintegrant for the formulation of double compressed tablets while rice starch was the worst disintegrant, in this study, as it significantly increased the hardness of tablets and showed a prolonged disintegration time as well as a poor dissolution rate. increasing the starch content of tablets resulted in a marked increase in their dissolution rate.     

Powder Compaction Properties of Sodium Starch Glycolate Disintegrants

ABSTRACT

The compaction behavior of three “as supplied” commercially available grades of sodium starch glycolate (SSG), Explotab, Primojel, and Vivastar P, was investigated at compression speeds of 0.17 and 30 mm/sec. The results suggested that the three “as supplied” materials exhibit different compression and compaction behavior. Primojel and Explotab exhibited similar compactibility, whereas Vivastar P produced compacts of poor integrity. This behavior was not mirrored in the compressibility of the powders, where Vivastar P and Explotab exhibited similar performance. The materials were studied using x-ray diffraction, scanning electron microscopy, Carr's compressibility index, and swelling volume. In terms of material characteristics, all the products exhibited similar swelling in water. Primojel and Explotab retained most of the crystallographic order from the parent potato starch and exhibited comparable particle surface topographies. Vivastar P contained the lowest moisture level. However, it is not clear if the poor compactibility of Vivastar P is due to differences in moisture content, the reduced surface topography, or subtle differences in the SSG polymer structures (substitution, cross-linking, and crystallinity). Overall, even though the three commercial grades of sodium starch glycolate are successfully used as disintegrants, they do exhibit differences in their “as supplied” powder mechanical properties: Primojel and Explotab exhibit similar compactibility, whereas Vivastar P is poorly compactable but exhibits similar compressibility to Explotab. These observations may have implications when formulating poorly compactable or moisture-sensitive drugs.     

Some Effects of Relatively Low Levels of Eight Tablet Disintegrants on a Direct Compression System

Eight common tablet disintegrants (Amberlite IRP-88, Corn Starch U.S.P. CLD, Explotab, Ac-Di-Sol, Sta-RX 1500 Starch, Polyplasdone XL, and Guar Gum) were used in concentrations of 0, 0.25, 0.5, 1 and 2% (w/w) in a direct compression system of 75:25 Unmilled Calcium Phosphate Dihydrate/Anhydrous Lactose. Using a Recording Powder Flowmeter (RPF) it was noticed that linearity of flow was relatively unaffected while g/sec. flow rate decreased with increasing concentrations. Each system was then lubricated and tableted keeping the applied pressure relatively constant. Evaluation of the resulting tablets showed that even at very low disintegrant concentrations, significant reduction in disintegration time took place. At the same time, very few detrimental effects often seen with tablet disintegrants, were noticed.     

Evaluation of Fast Disintegrants in Terfenadine Tablets Containing a Gas-Evolving Disintegrant

Abstract

Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaC0₃, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone < Ac-Di-Sol < Primojel < low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.     

The Swelling & Water Uptake of Tablets III: Moisture Sorption Behavior of Tablet Disintegrants

Water vapor sorption properties and the thermal behavior of four disintegrants including microcrystalline cellulose (Avicel PH102), croscarmellose sodium (Ac-di-sol), corn starch, and sodium starch glycolate (Primojel), were studied. They all exhibited type II-like isotherm. The apparent monolayer sorption for each of disintegrants was found to be significantly greater than the specific surface obtained from nitrogen adsorption. It is proposed that water molecules interact with specific sites on the disintegrant glassy polymer. Water tends to stay as a condensed phase on the polymer, rather than to diffuse into the bulk. Water plasticization caused glass transition temperature (T_g) of all disintegrant polymers to decrease. It facilitated a change from glass to the rubber state. Because the sorption sites were in the glassy state, the change from glass to rubber, which in turn kinetically reduced the available sites, would reflect the sorption capacity of a disintegrant polymer. In addition, the difficulty in freezing a disintegrant's sorbed water was encountered.     

Frictional Properties of Tablet Lubricants

Some frictional properties of tablet lubricants were determined. The friction coefficients and the adhesion forces of six lubricants were evaluated by the method proposed previously. The ejection force against the radial force for each lubricant yielded a straight line through the origin, so that the adhesion forces of these lubricants were estimated to be almost zero. All lubricants had low friction coefficients when they alone were compressed. The value for metal stearate was the smallest and that for talc was the largest. The affinity of the lubricants to the die wall, another important property of the lubricants, was also determined. After the die wall was conditioned by the tabletings of each lubricant alone, the serial tabletings of lactose granulates in the die were carried out. The increasing rate of ejection force in the conditioned die in a serial tableting was different for every pretreatment of each lubricant. The affinity of magnesium stearate to the die wall surface was superior to that of other lubricants.     

Frictional Properties of Tablet Lubricants

Abstract

Some frictional properties of tablet lubricants were determined. The friction coefficients and the adhesion forces of six lubricants were evaluated by the method proposed previously. The ejection force against the radial force for each lubricant yielded a straight line through the origin, so that the adhesion forces of these lubricants were estimated to be almost zero. All lubricants had low friction coefficients when they alone were compressed. The value for metal stearate was the smallest and that for talc was the largest. The affinity of the lubricants to the die wall, another important property of the lubricants, was also determined. After the die wall was conditioned by the tabletings of each lubricant alone, the serial tabletings of lactose granulates in the die were carried out. The increasing rate of ejection force in the conditioned die in a serial tableting was different for every pretreatment of each lubricant. The affinity of magnesium stearate to the die wall surface was superior to that of other lubricants.     

Evaluation of Different Fast Melting Disintegrants by Means of a Central Composite Design

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X₁) and the compression force (X₂). These factors were studied for tablets containing either Zeparox® or Pearlitol 200® as soluble diluents and six different disintegrants: L-HPC® LH11 and LH31, Lycatab PGS®, Vivasol®, Kollidon CL®, and Explotab®. Their micromeritics properties were previously determined. The response variables were disintegration time (Y₁), tensile strength (Y₂), and porosity (Y₃). Whatever the diluent, the longest disintegration time is obtained with Vivasol® as the disintegrant, while Kollidon CL® leads to the shortest disintegration times. Exception for Lycatab PGS® and L-HPC LH11®, formulations with Pearlitol 200® disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox® as the diluent when compared to Pearlitol 200® and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS® concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200® is used with Vivasol®, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox®, the interaction between the two controlled variables is more complex: there is no effect of compression force on the disintegration time for a small amount of disintegrant, but a significant increase for higher concentrations. With Kollidon CL®, the main factor influencing the disintegration time is the compression force, rather than the disintegrant concentration. Increasing both the compression force and the disintegrant concentration leads to an increase of the disintegration time.For lower Kollidon CL® percentages, the compression pressure increases dramatically the tablet disintegration. With the Explotab®, whatever the increase of compression force, the disintegrant concentration leads to an increase of the disintegration time. According to Student's t-test, only the compression force significantly and strongly influences the disintegration time when Pearlitol 200® is used. A slight interaction and some trends nevertheless appear: above 150 MPa, increasing the disintegrant concentration leads to a shortened disintegration time, below this limit the opposite effect is observed.     

Disintegrating Force and Tablet Properties

The development of a disintegrating force inside the tablet due to the liquid/solid contact depends on a proper wetting of the material and occur according to saturation kinetics.

The aim of the present work is the evaluation of such a force development in relation to the characteristics of the tablet in particular to the compression force.

For this purpose, the disintegrating force of different tablets formulations has been measured by means of a previously described apparatus.

The results obtained show that a new evaluation of a compact disintegration characteristics may be obtained through the determination of such parameters as the maximum force developed (y₀) and the time of the half maximum force development (b).     

Evaluation of Bilayer Tablet Machines—A Case Study

Four bilayer tablet compression machines were evaluated for their suitability for compression of a specific bilayer tablet formulation. Tablet machines evaluated were: Manesty (Model No. BB4), Manesty (Model No. Rotappress), Fette (Model No. P3102) and Kilian (Model No. 51AST-ZS) tablet presses. The tablet delamination tendency was the primary acceptance criteria for the evaluation of tablet press performance. The compression force on layer I was found to be the major factor influencing tablet delamination. It was found that the Kilian press was best suited for the compression of the model bilayer tablet formulation. The Kilian press is equipped with a special sampling device for layer I which allows additional compression force to be applied on layer I only at the time of weight sampling. The sampling device then returns to the original set points after sampling is completed. This feature maintains the compression force on layer I to a minimum during routine compression. Data indicated that the compression force on layer I and the compression zone in the die cavity of layer II were two factors needing to be controlled in order to yield bilayer tablets with acceptable physical characteristics.     

A Comparative Study of the use of Enset and Potato Starches in Tablet Formulations

Enset and potato starches have been compared as binding agents and disintegrants in tablets made with paracetamol and chloroquine phosphate. Tablet crushing strengths, friabilities and disintegration times have been measured. The results show that enset starch can be used both as a binding agent and disintegrant. It has a better binding ability than potato starch, giving tablets of lower porosity. However because of this, tablets containing enset starch disintegrate more slowly.     

Comparative Tablet and Rheological Properties of New Microcrystalline Cellulose: Direct Compression and Wet Granulation Methods

The overall objective of this study was to compare the rheological properties and tablet characteristics of two new varieties of celluloses (Vivacel 101 and 102), recently produced and commercialized, with the classical varieties of celluloses (Avicel and Elcema). The results showed no significant differences in the rheological properties of Vivacel and Avicel, while significant differences were found between the two celluloses and Elcema. Furthermore, there were no statistically significant differences in the disintegration times and T_d values of Vivacel and Avicel. In conclusion, it was found that these new celluloses offer all the known advantages of Avicel.     

Effect of Micronization of Norfloxacin on Tablet Properties

The particle size of norfloxacin was reduced through the use of an air attrition mill. Not unexpectedly, this treatment also increased the surface area of the drug. Granulations were then prepared from nonmicronized as well as micronized drug. Tablets were compressed from each of these granulations and their physicochemical properties determined. Tablets containing micronized drug showed faster in-vitro dissolution rates and an improvement in bioavailability when tested in Rhesus monkeys.     

Effect of Micronization of Norfloxacin on Tablet Properties

Abstract

The particle size of norfloxacin was reduced through the use of an air attrition mill. Not unexpectedly, this treatment also increased the surface area of the drug. Granulations were then prepared from nonmicronized as well as micronized drug. Tablets were compressed from each of these granulations and their physicochemical properties determined. Tablets containing micronized drug showed faster in-vitro dissolution rates and an improvement in bioavailability when tested in Rhesus monkeys.     

Comparative Bioavailability Study of Two Controlled-Release Pentoxifylline Tablet Preparations

The bioavailability of a generic preparation of pentoxifylline sustained-release (SR) tablet was evaluated in comparison with a proprietary product (Trental 400®). For the study, 12 healthy male volunteers participated; the study was conducted according to a randomized, two-way crossover design. The bioavailability was compared using the parameters total area under the plasma level-time curve AUC_0?∞, peak plasma concentration C_max, and time to reach peak plasma concentration T_max. No statistically significant difference was observed between the values of the two products in all three parameters. The 90% confidence interval for the ratio of the logarithmic transformed AUC_0?∞ values of the generic pentoxifylline over those of Trental 400 was found to lie between 0.83 and 1.00, while that of the parameter C_max was between 0.91 and 1.29. In addition, elimination half-life t_1/2 and apparent volume of distribution V_d were calculated. There was no statistically significant difference between the t_1/2V_d values obtained from the data of the two preparations.     

Comparative Bioavailability Study of a Generic Naltrexone Tablet Preparation

The bioavailability of a generic preparation of naltrexone (Narpan) was compared with the innovator product, Trexan. Twelve healthy volunteers participated in the study, conducted according to a completely randomized, two-way crossover design. The preparations were compared using the parameters area under the plasma concentration–time curve AUC_0–∞, peak plasma concentration C_max, and time to reach peak plasma concentration T_max. No statistically significant difference was observed between the logarithmic transformed AUC_0–∞ and the logarithmically transformed C_max values of the two preparations. Also, no statistically significant difference was observed between the untransformed T_max values. In addition, the 90% confidence interval for the ratio of the logarithmic transformed AUC_0–∞ values of Narpan over those of Trexan was found to lie between 0.87 and 1.01, while that of the logarithmic transformed C_max values was between 0.94 and 1.23, both being within the bioequivalence limit of 0.80–1.25. The numerical values of the elimination half-life (t_1/2) obtained with the two preparations were also not significantly different and were comparable to those reported in the literature.     

A Method for Quantitative Evaluation of the Effectiveness of tee Lubricants Used in Tablet Technology

Modern formulation bases the appropriate selection of excipients on technological determinations. Due to negative effects on mechanical and biopharmaceutical properties of tablets, the amount of lubricant to be used requires optimization. Lubricants are difficult to evaluate in terms of effectiveness. The number of references existing in literature on this topic substantiates the necessity still remaining in pharmaceutics for lubricant testing (1, 2, 3, 4, 5).     

Evaluation of Surface and Bulk Characteristics of Cellulose I Powders in Relation to Compaction Behavior and Tablet Properties

Abstract

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.