A Combination Disintegration-Dissolution Apparatus for Fast-Disintegrating

Abstract

A combination disintegration-dissolution apparatus for fast disintegrating tablets is described. Preliminary investigation using sodium carboxymethyl starch as the disintegrant indicated that the apparatus was capable of detecting differences in the disintegration time both due to disintegrant concentration as well as due to the intensity of agitation used in the apparatus. No difference in the disintegration times could be observed when similar tablets were evaluated using the existing disintegration apparatus.

The combination apparatus described is simple in construction and design and can be fabricated quite easily and economically in the laboratory. Due to the anticipated increase in the availability of fast-disintegrating tablets, this apparatus will be useful to the pharmaceutical formulator as a valuable quality control tool. In addition, the apparatus is adaptable to various other agitational systems in common usage and can be used by laboratories carrying out combined disintegration and dissolution tests using automated equipment.     

Evaluations of the Mechanism of Disintegrant Action

The disintegrant properties of eight tablet disintegrants (a cation exchange resin, cross-linked carboxymethyl cellulose, sodium starch glycolate, U.S.P., Crospovidone, U.S.P., corn starch, an insoluble anionic cellulose polymer, a modified food starch, and a soybean cellulose derivative) have been evaluated. Three techniques were applied to some or all of the materials. Water uptake rates and capacities were determined for all disintegrants in bulk powders. Disintegration times of tablets formulated with varying concentrations of the different disintegrants in a matrix comprising 75% unmilled dibasic calcium phosphate dihydrate and 25% anhydrous lactose were measured. For four disintegrants, a novel computer assisted cinsphotomicrographic technique was applied to investigate the interaction of water with individual disintegrant particles, both in terms of swelling rate and maximum water capacity

Comparative evaluation of tablet disintegrants and studies of the mechanism of disintegrant action have quite properly attracted the attention of a number of pharmaceutical scientists. (1-16) However, it is clear that at present there is no concensus concerning a general theory rationalizing disintegrant action and at least five separate mechanism have been proposed (1, 2, 4)

In the present paper, the disintegrant action of eight disintegrants has been studied using three separate approaches. Firstly, the rate and capacity of the bulk powders to take up water and to swell as a result has been evaluated using an apparatus similar to that used by Nogami and coworkers (5). Secondly, the disintegration times of tablets containing varying concentrations of disintegrant and compressed using a matrix of 75% unmilled dibasic calcium phosphate dihydrate and 25% anhydrous lactose were determined in a manner similar to that described by Rudnic and his associates (6). Thirdly, the authors are able to report - apparently for the first time - the use of a new method for evaluating the rate and extent of swelling of individual units in an assembly of disintegrant particles. This method exploits a cinephotomicrographic technique in which groups of disintegrant particles are photographed under a microscope by a high speed movie camera with the resultant film being analyzed by a special computer technique which allows the size of both individual and all particles, in any given visual field, to be followed over the very short period of time which elapses during the interaction of the disintegrant particles with water. The results presented in this paper demonstrate that a combination of the three methods described above and, in particular, the computer assisted cinemicrophotographic technique allow considerable insight to be gained of the disintegration process     

The Effect of Recompression on the Dissolution of Wet Massed Tablets Containing 'Super' Disintegrants

The effect of recompression on the disintegration, and dissolution of tablets employing 'super' disintegrants within a wet-massed Avicel matrix is reported. Differences were found in the disintegration times of tablets containing intra-granular or extra-granular disintegrants (Polyplasdone XL, Explotab and Ac-di-sol), both between disintegrant type and within the same disintegrant system following rework.

In the case oE extra-granular disintegrant, reworked compacts dissolved faster than the first compression tablets, irrespective of disintegrant type. Thus, milling and dispersion of the drug during rework appear to dominate over the effects of impaired disintegration when 'super' disintegrants are present. The control compacts (no disintegrant), however, dissolved less quickly following rework, indicating that dissolution was controlled by disintegration.

Tablets with intra-granular Polyplasdone XL and Ac-di-sol dissolved less quickly following rework. Both disintegrants have poor intra-granular rework efficiencies. However, for Explotab, which has better rework intra-granular efficiency, reworked tablets dissolved faster than first compression compacts.     

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.     

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.     

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.     

The Effect of Recompression on the Dissolution of Wet Massed Tablets Containing ‘Super’ Disintegrants

The effect of recompression on the disintegration, and dissolution of tablets employing ‘super’ disintegrants within a wet-massed Avicel matrix is reported. Differences were found in the disintegration times of tablets containing intra-granular or extra-granular disintegrants (Polyplasdone XL, Explotab and Ac-di-sol), both between disintegrant type and within the same disintegrant system following rework.

In the case oE extra-granular disintegrant, reworked compacts dissolved faster than the first compression tablets, irrespective of disintegrant type. Thus, milling and dispersion of the drug during rework appear to dominate over the effects of impaired disintegration when ‘super’ disintegrants are present. The control compacts (no disintegrant), however, dissolved less quickly following rework, indicating that dissolution was controlled by disintegration.

Tablets with intra-granular Polyplasdone XL and Ac-di-sol dissolved less quickly following rework. Both disintegrants have poor intra-granular rework efficiencies. However, for Explotab, which has better rework intra-granular efficiency, reworked tablets dissolved faster than first compression compacts.     

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.     

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.     

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.     

Studies of the Utility of Cross Linked Polyvinlpolypyrrolidine as a Tablet Disintegrant

Studies of different particle size grades of cross linked polyvinylpolypyrrolidone (Polyplasdone G.A.F. Corporation) In direct compression tablet formulations show that Increase in mean particle size enhances powder flow, disintegration and dissolution although hardness and friability were slightly better for tablets made from the finer grades. The disintegrant exhibits powerful disintegrant action at low concentrations. It should probably be rarely, if ever, necessary to use more than five per cent in a tablet in order to achieve rapid dissolution. It appears that the use of polyvinylpolypyrrolidone (P.V.P.P.) as a tablet disintegrant at high concentrations may be self limiting since certain properties such as powder flow, tablet weight variation, hardness and friability start to reach unacceptable levels at high disintegrant concentrations. Data presented in this paper indicates that tablets con-taining acetylsalicylic acid or multi-vitamins can be very effec-tively formulated using P.V.P.P. as a disintegrant.     

The Influence of the Swelling Characteristics of Starch and Starch Derivates on the Disintegration of Powders, Packed in Hard Gelatin Capsules

Starch and starch derivates are frequently used in tablets to improve the disintegration. Their disintegrating action has mainly been attributed to the swelling of the particles when they are immersed in an aqueous solution. It has been assumed that tablet disintegration would be related to the ratio between the pore diameter and the linear growth of the disintegrant particles. The present work investigates the relationship between disintegrant swelling, pore diameter and drug release rate for loosely packed powderbeds in hard gelatin capsules.     

Comparative Study of Disintegrating Agents in Tiaramide Hydrochloride Tablets

Abstract

The water sorption properties of some commonly used disintegrants (i.e., starch, sodium starch glycolate, croscarmellose sodium, crospovidone and alginic acid) were studied to correlate the disintegration and physical mechanical properties of tiaramide hydrochloride tablets containing 5% of these disintegrants. With the exception of alginic acid, disintegration time of tablets decreased with the increase in water sorption properties of the disintegrants.When exposed to high humidity (100% RH at 35°C), tablets containing two high water-sorbing disintegrants, e.g., croscarmellose sodium and crospovidone, exhibited a marked decrease in hardness. When these tablets were dried after exposure to humidity, the hardness remained lower than the initial values. It is possible that high water affinity of the disintegrants disrupts the interparticulate bonds inside the tablets. However, such a decrease in interparticulate bond may not be observed if the disintegrant also acts as a binder in the presence of water. For example, the hardness of tablets containing another high water-sorbing disintegrant, sodium starch glycolate, increased when these tablets dried after exposure to high humidity. Unlike croscarmellose sodium and crospovidone, sodium starch glycolate also increased the disintegration time if tablets were previously exposed to high humidity. Studies of the moisture absorption and drying cycle may be very important in evaluating environmental effects of tablets containing high watersorbing disintegrants.     

The Influence of the Swelling Characteristics of Starch and Starch Derivates on the Disintegration of Powders,Packed in Hard Gelatin Capsules

Abstract

Starch and starch derivates are frequently used in tablets to improve the disintegration. Their disintegrating action has mainly been attributed to the swelling of the particles when they are immersed in an aqueous solution. It has been assumed that tablet disintegration would be related to the ratio between the pore diameter and the linear growth of the disintegrant particles. The present work investigates the relationship between disintegrant swelling, pore diameter and drug release rate for loosely packed powderbeds in hard gelatin capsules.     

Response surface analysis applied to the preparation of tablets containing a high concentration of vegetable spray-dried extract

This work relates to the formulation of tablets containing a high proportion of spray-dried extracts (SDEs) from Passiflora edulis leaves. The tablets were prepared by direct compression. Colloidal silicon dioxide was selected as a glidant and moisture adsorbent, cross-linked carboxymethycellulose was used as the disintegrant, microcrystalline cellulose was the filler/binder, and tricalcium phosphate as a spray-drying adjuvant. The colloidal silicon dioxide and cross-linked carboxymethycellulose quantities and their influences on the tablet hardness and disintegration time were studied by a central composite design. The model equations were fitted to the experimental data and then validated. It could be concluded that the colloidal silicon dioxide proportion increased the hardness, and the cross-linked carboxymethycellulose proportion determined a linear decrease of the disintegration time. The optimal values chosen were 2.0% Aerosil® 200 and 2.5% Ac-Di-Sol®. The tablets showed a hardness of 85.02 N and a disintegration time of 7.35 min.     

The Effect of Recompression on the Swelling Kinetics of Wet Massed Tablets, Containing 'Super' Disintegrants

The effect of recompression on the swelling force kinetics of tablets employing a wet massed Avicel matrix and those containing extra-granular super disintegrants has been investigated. Explotab, unlike the Ac-Di-Sol and Polyplasdone XL systems, was found to give a high initial compact swelling force at low tablet porosities, but the rework process reduced the maximal swelling forces for all systems. However, the measured maximal swelling forces did not correlate with tablet disintegration time.

The rate of fluid penetration into the compacts was found to be controlled by tablet porosity but the penetration rates for all disintegrant systems were essentially identical. However the penetration rates for reworked compacts were significantly lower than those for tablets produced by first compression possibly due to the effects of increased lubricant distribution and relubrication causing poorer wettability.

Tablet disintegration times were found to correlate with a fluid penetration kinetic function involving lag time and time for 50% tablet swelling. Also, the retention of disintegration efficiency following rework correlated with the retention of the rate of fluid penetration. It is concluded that lubricants can play an important role in the efficiency of compact disintegration following tablet rework.     

Investigation of Prolonged Drug Release from Matrix Formulations of Chitosan

A hydrocolloidal matrix system containing complexes of chitosan was investigated for preparation of sustained release tablets and examined in-vitro.

Theophylline tablets using chitosan as a sustained release base were evaluated. It was found that when chitosan is used in a concentration of more than 50% of tablet weight, an insoluble non-erosion type matrix was formed. Tablets prepared with a chitosan concentration of less than 33% were fast releasing.

Chitosan used in a concentration of about 10% acted as a disintegrant and the drug was dissolved within an hour.

Citric acid slowed down the release rates of chitosan based theophylline tablets. Theophylline tablets using carbomer-934P as a sustained release base were evaluated. Carbomer-934P in lower concentrations forms an erosion type matrix. In order to produce a twenty-four (24) hour sustained release tablet, more than 10% concentration of carbomer-934P is needed. Combination with chitosan and carbomer-934P produced slower releasing tablets.

A hydrocolloidal erosion type matrix was formulated using chitosan, carbomer-934Pand citric acid. Only 10% of chitosan was needed to prepare theophylline sustained release tablets in these mixtures.

The dose dumping potential of chitosan tablets due to rapid disintegration in alkaline media was eliminated by preparing hydrated erosion type matrix systems.     

Response Surface Analysis Applied to the Preparation of Tablets Containing a High Concentration of Vegetable Spray-Dried Extract

This work relates to the formulation of tablets containing a high proportion of spray-dried extracts (SDEs) from Passiflora edulis leaves. The tablets were prepared by direct compression. Colloidal silicon dioxide was selected as a glidant and moisture adsorbent, cross-linked carboxymethycellulose was used as the disintegrant, microcrystalline cellulose was the filler/binder, and tricalcium phosphate as a spray-drying adjuvant. The colloidal silicon dioxide and cross-linked carboxymethycellulose quantities and their influences on the tablet hardness and disintegration time were studied by a central composite design. The model equations were fitted to the experimental data and then validated. It could be concluded that the colloidal silicon dioxide proportion increased the hardness, and the cross-linked carboxymethycellulose proportion determined a linear decrease of the disintegration time. The optimal values chosen were 2.0% Aerosil® 200 and 2.5% Ac-Di-Sol®. The tablets showed a hardness of 85.02 N and a disintegration time of 7.35 min.     

Evaluation of sorghum starch as a tablet excipient

The suitability of sorghum starch as a binder and disintegrant at various concentrations in diverse tablet formulations have been investigated. Sodium bicarbonate and calcium carbonate were used as soluble and insoluble inorganic medicinal substances in various tablet formulations.

The effect of sorghum starch on the physical properties of the tablets were compared with those formulated with maize starch using the same concentrations of binder and disintegrant under the same experimental conditions.

The observations show that sorghum starch can be used as binder and disintegrant in tablet formulations. The indication is that the starch exhibit about twice the disintegrant power and about the same binding efficacy compared to maize starch.     

A Contribution to the Manufacture of Diiodoquin TABLETS by Direct Compression

Six direct compression vehicles and their binary blends in ratios of 1:1, 1:3 and 3:1 were investigated to compress diiodoquin directly into tablets. With respect to the mechanical properties of the produced tablets, Avicel, Celutab and 5TAR-x1500 were the suitable single vehicles for the manufacturing. Five vehicles, except STAR-x1500, produced tablets of fairly long disintegration times (120 min), while the other vehicle could not compress diiodoquin. The results shewed that blending of Avicel or Celutab with STAR-x1500 improved the physical standards of the produced tablets. Other than being a powerful disintegrant, STAR-x1500 could recover the disintegrating effect of Avicel. On the other hand, the reduction in disintegration times of the tablets compressed with STAR-/Celutab blends, was due to the incorporation of STAR-x in the formulations.

In such a case of noncompressible drug, a large concentration of a binary blended vehicle was needed to compress tablets of good physical characters. The least concentration needed to compress diiodoquin into tablets was not less than 42.0% w/w.