Carboxymethylstarches in Wet Granulation

Commercialized carboxymethystarches (CMS) are both carboxyme-thylated and cross linked potato starch.

The influence of carboxymethylation and cross linkage on the disintegrating properties of starch are studied.

Tablets are made with acetaminophen as drug, Emcompress as diluant, Magnesium stearat as lubricant, and potato starch or its derivatives as disintegrants.

Tablets are prepared by direct compression or by wet granulation with the disintegrant intervening only in internal phasis.

Five disintegrants were studied, with two different concentrations:

native potato starch

potato starch simply cross linked

potato starch simply carboxymethylated

two potato starches both cross linked and carboxymethylated at two different degrees

Compressibility of powders blending and grain for compression are discussed.

The hardness, the tablet disintegration and the rate of drug dissolution are studied.

The results showed that the simply carboxymethylated starch has a totally different behaviour after direct compression or wet granulation. The poor results after wet granulation could be imputed to the bursting of starch granules during grain drying. Since it has lost its granular structure, the carboxymethylated starch will only allow a poor disintegration and a slow dissolution of the drug.

A very similar behaviour of native and simply cross linked starch: the results of which are bad for tablets either prepared by wet granulation or direct compression.

A very similar behaviour of the starches both carboxymethylated and cross linked, allowing a very good disponibility, either with tablets prepared by direct compression or wet granulation. These experiments prove :

the need for an sufficient cross linkage for CMS in a wet granulation process     

Moisture-Activated dry Granulation in a high Shear Mixer

Abstract

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

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

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 that 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.     

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.     

Chitin and Chitosan as Disintegrants in Paracetamol Tablets

Abstract

Chitin and chitosan as disintegrants in paracetamol tablets were evaluated and compared to four commonly used disintegrants. Tablets containing chitosan showed faster disintegration, greater dissolution and was slightly softer than those containing chitin. An increment in concentration of these polymers caused markedly faster disintegration and better dissolution while an increase in compressional force showed opposite effects. Aging slightly altered the disintegration and dissolution. Tablets containing 7% of chitosan disintegrated within one minute which was much faster than those containing corn starch and microcrystalline cellulose but slightly slower than those containing sodium starch glycolate and croscamellose sodium. However, their dissolution profiles were non-significantly different from those of the latter ones.

Crystallinity, degree of acetylation, chain length and particle size were attributed to the efficiency of chitin and chitosan. Moisture sorption and water uptake were found to be the major mechanisms of disintegration while dissolution related to the swelling capacity.     

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.     

Study on Tablet Binding and Disintegrating Properties of Alternative Starches Prepared from Taro and Sweet Potato Tubers

To demonstrate the potential alternative sources of starch used in tablet formulations, starches from taro (TS) and sweet potato (SPS) tubers were prepared with obtained yields of 11.0 and 9.6%, respectively. Both TS and SPS met USP22-NF17 identification and specifications. Their equilibrium moisture contents and gelatinization temperatures were comparable with those of commercial starch, whereas amylose contents of TS and SPS were 21.38% w/w and 41.76% w/w, respectively. Both were found to possess similar flow characteristics. To evaluate TS and SPS as granulating agents and disintegrants, tablets with controlled compression loads were prepared by incorporating a starch candidate with dibasic calcium phosphate in paste and powders forms, respectively. Tablets were then evaluated based on compressibility, friability, and disintegration. It was found that the binding and disintegrating performance of both TS and SPS was similar to that of commercial cornstarch.     

Study on tablet binding and disintegrating properties of alternative starches prepared from taro and sweet potato tubers

To demonstrate the potential alternative sources of starch used in tablet formulations, starches from taro (TS) and sweet potato (SPS) tubers were prepared with obtained yields of 11.0 and 9.6%, respectively. Both TS and SPS met USP22-NF17 identification and specifications. Their equilibrium moisture contents and gelatinization temperatures were comparable with those of commercial starch, whereas amylose contents of TS and SPS were 21.38% w/w and 41.76% w/w, respectively. Both were found to possess similar flow characteristics. To evaluate TS and SPS as granulating agents and disintegrants, tablets with controlled compression loads were prepared by incorporating a starch candidate with dibasic calcium phosphate in paste and powders forms, respectively. Tablets were then evaluated based on compressibility, friability, and disintegration. It was found that the binding and disintegrating performance of both TS and SPS was similar to that of commercial cornstarch.     

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.     

The Effect of Recompression on Disintegrant Efficiency in Tablets Prepared by wet Granulation

Abstract

The efficiency of three modern disintegrants, Explotab, Ac-Di-Sol and Polyplasdone XL, has been investigated following rework of a wet massed, slowly eroding, tablet formulation. When the disintegrants were placed extra-granularly it was found that only Explotab retained good efficiency following rework. All disintegrants placed intra-granularly had rework efficiencies that were essentially the same as the control (no disintegrant). However, the addition of 2% extra-granular disintegrant prior to the second compression restored tablet disintegration behaviour for Polyplasdone XL and partially for Ac-Di-Sol.

Two of the factors potentially affecting the reworkability of disintegrants (comminution and regranulation) were also investigated. Regranulation caused Ac-Di-Sol and Explotab to significantly lose disintegrant efficiency. However milling alone caused no reduction in efficiency of any disintegrant.     

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.     

Aging of Tablets Prepared by Direct Compression of Bases with Different Moisture Content

Abstract

Properties of aged tablets prepared by the wet granulation method were found to be affected by the moisture content of the granules. In this study, the storage-induced changes in hardness, disintegration and drug release were evaluated for tablets made by direct compression of three different bases with different initial moisture content. Tablets with high initial moisture content were found to increase in hardness upon storage. The magnititude of such increase is dependant upon the physical properties of the base and the absolute moisture content. The increase in hardness may increase the disintegration time and decrease drug release. Tablets with low initial moisture content were minimally affected by storage. The gain of moisture by some of these tablets led to enhancement in disintegration and drug release. Among the tablets studied lactose based tablets with different initial moisture content were found to be the most resistant to changes upon storage.     

Factors Affecting Rate of Dissolution of Prednisone from Tablets

Abstract

A study was carried out to evaluate some parameters which may have an effect on the dissolution rate of prednisone from tablets. The parameters examined involving formulation were: diluent proportion (Lactose-starch), dissintegrant type (starch, explotab (sodium starch glycolate) type of binder (starch paste, gelatine water solution and PVP alcoholic solution), lubricant, and dye concentration. The Manufacturing variables studied were: method of manufacture (wet granulation, direct compression and double compression), granule size in wet granulation and tablet hardness. dissolution profiles of tablets storaged 2 months at 45°C were compared with those of fresh samples. Tablets prepared with prednisone five years old, tablets with fresh active ingredient and tablets with two different prednisone concentrations (5 and 50 mg per tablet) were used for other evaluations.

In all cases micronized prednisone was used and all batches were physically and chemically evaluated before studying their dissolution following the USP basket method.

The parameters studied that affected significatively dissolution rate of prednisone were: type of binder, lubricant concentration, method of manufacture, active ingredient, age and prednisone concentration.     

Effects of Process Variables and Excipients on Tabletting Parameters of Norfloxacin Tablets

Abstract

A study was conducted to evaluate the tabletting parameters of Norfloxacin (NIX) tablets. The effects of method of tabletting. e.g., direct compression, dry granulation and wet granulation, moisture content and water soluble/insoluble additives on final hardness, disintegration and dissolution of the tablets were investigated.     

Disintegration and Dissolution Parameters of Compressed Tablets Prepared by Direct Compression-Wet Granulation Process and Compression of Wet Granulation of Both Sections

Abstract

Hardness, disintegration and dissolution of compressed tablets were assessed by compressing tablets from granulations prepared by dry and wet granulation process of two sections and by composite wet granulation process. Modified USP XVIII apparatus for disintegration, rotating basket apparatus USP XVIII and constant circulation apparatus were employed for measuring dissolution. The constant circulation apparatus was used in the studies as only it proved to be sensitive to reflect the differences in the dissolution rates and was a close analog of physiological situation. Four types of tablets containing acetylsalicylic acid, codeine phosphate and propoxyphene hydrochloride were prepared. Tablets prepared by partial dry and wet granulation process did not show significant differences in the rates of dissolution as compared to those prepared by complete wet granulation process.     

Physical Properties and Stability of Diazepam and Phenobarbitone Sodium Tablets Prepared with Compactrol

Abstract

Compactrol as a newly introduced direct compressible vehicle was used for the preparation of Diazepam and phenobarbitone sodium tablets. Spray dried lactose and wet granulation technique were also employed to prepare these tablets for comparison. The effect of storage at 75% RH, at two temperature levels (25° and 45°) on the physical properties of these tablets was studied for 6 weeks. It was found that, there were an increase in tablet weight, thickness and friability per cent, while a significant decrease in hardness was observed. Tablets prepared with compactrol showed no significant changes in both disintegration and dissolution times, while tablets prepared with spray dried lactose showed a marked decrease in disintegration and dissolution times. On the other hand, tablets prepared by wet granulation showed a pronounced in crease in both disintegration and dissolution times.     

The Effect of Molecular Structure on the Function of Sodium Starch Glycolate in wet Granulated Systems

The effect of variation in the degree of cross-linkage and extent of substitution on the disintegrant properties of sodium starch glycolate in wet granulated systems has been examined. The rates of mixing shear were evaluated for their effect on the ability of the disintegrants to function after granulation. In addition, the effect of varying the intragranular and extra-granular concentration of the disintegrants was investigated. The results indicate that increased rates of mixing shear adversely effect sodium starch glycolates. In addition, the current commercial specifications for a marketed sodium starch glycolate seem to be optimal in this segard. It also seems evident that a mixture of disintegrant within and around the granule is desirable in wet granulated systems.

Previous papers have discussed the importance of raw materials specifications in defining the fitness for use of many pharmaceutical excipients (1-6). We have recently initiated a study concerning the effect of variation of degree of cross-linkage and extent of substitution on the disintegrant action of sodium starch glycolate in direct compression systems. Further details of this study will be provided in a paper focussed on standard raw materials tests for disintegrants and their relative differences in direct compression systems (7).     

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.     

Formulation strategy towards minimizing viscosity mediated negative food effect on disintegration and dissolution of immediate release tablets

Food induced viscosity can delay disintegration and subsequent release of API from solid dosage form which may lead to severe reduction in the bioavailability of BCS type III compounds. Formulations of such tablets need to be optimized in view of this postprandial viscosity factor. In this study, three super disintegrants, croscarmellose sodium (CCS), cross-linked polyvinylpolypyrrolidone (CPD), and sodium starch glycolate (SSG) were assessed for their efficiency under simulated fed state. Tablets containing these disintegrants were compressed at 10 and 30?KN, while taking lactose as a soluble filler. In addition to other compendial tests, disintegration force of these formulations was measured by texture analysis. Comparison of parameters derived from force – time curves revealed a direct relation of maximum disintegration force (F_max) and disintegration force development rate (DFDR) with compressional force in fasted state, whereas an inverse relationship of F_max and DFDR with compressional force was observed in fed state. The gelling tendency of disintegrants influenced the rate of release of API in simulated fed and fasted states when compressional force was changed. These observations recommend the evaluation of formulations in simulated fed state, in the development stage, with an objective of minimizing the negative impact of food induced viscosity on disintegration. Use of disintegrants that act without gelling or can counteract the effect of gelling is recommended for tablet formulations with reduced disintegration time (DT) and mean dissolution time (MDT) in fed state, respectively.     

Optimization of Tablet Formulations Based on Starch/Lactose Granulations for Use in Tropical Countries

Abstract

Several granulations consisting of α-lactose monohydrate 200 mesh and native starch (corn, potato, rice or tapioca) were prepared. The influence of starch concentration, storage temperature and relative humidity on the physical properties of the tablets prepared from these granulations was estimated. Two granulations, which resulted in tablets with adequate initial values of crushing strength and disintegration time and with an acceptable physical stability were selected as standard granulations. The selected standard granulations were evaluated by incorporating a drug (diazepam, 2 mg or mebendazole, 100 mg). The tablet properties were determined one day after preparation. The crushing strength, the disintegration time and the microbiological quality were also measured after storage under tropical conditions. Both selected formulations proved to be adequate for the preparation of tablets by wet granulation, suitable for use in tropical countries.