Carboxymethylstarches in Wet Granulation

Abstract

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     

An evaluation of starch obtained from pearl millet - Pennisetum typhoides. As a binder and disintegrant for compressed tablets

The binding and disintegrant properties of millet starch obtained from Pearl Millet - Pennisteum typhoides (Staph. Burn, and Hubb.) Fam. Gramineae have been evaluated using tablet formulations of four drugs.

The results showed that Millet starch compared favourably with Maize starch with regards to most of the parameters used to evaluate the tablets. It can be safely concluded that millet starch is suitable for use as a binder and disintegrant in tablet formulations.     

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     

An evaluation of starch obtained from pearl millet - Pennisetum typhoides. As a binder and disintegrant for compressed tablets

Abstract

The binding and disintegrant properties of millet starch obtained from Pearl Millet - Pennisteum typhoides (Staph. Burn, and Hubb.) Fam. Gramineae have been evaluated using tablet formulations of four drugs.

The results showed that Millet starch compared favourably with Maize starch with regards to most of the parameters used to evaluate the tablets. It can be safely concluded that millet starch is suitable for use as a binder and disintegrant in tablet formulations.     

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.     

Effect of Particle Size and Excipients on the Dissolution Rate of Metronidazole from Solid Dosage Forms: II

In-vitro dissolution tests were carried out with tablets prepared from different particle size ranges of metronidazole. Influence of tablet binding agents (Methylcellulose, polyvinyl pyrrolidone - (PVP), potato starch and gelatin) on the drug release were investigated under similar conditions. Comprimates containing PVP and drug with particle size 1.75 μm (in lactose mixture) gave optimum results. These findings may open new ways of formulating a metronidazole tablet exhibiting improved drug - liberation, subsequently with a better bioavailability than the KUON^R-Tablet manufactured in Hungary.     

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.     

The Effect of Four Tablet Binders on the Bioavailability of Frusemide from 40MG Tablets

Tablets containing frusemide 40mg have been prepared using four different binders; polyvinylpyrrolidone, starch mucilage, stearic acid and methylhydroxyethyl cellulose. With the exception of the tablets prepared using stearic acid, all the tablets disintegrated in under 2 minutes and exhibited hardnesses ranging from 12 to 17 s.c.u. The dissolution rate, measured in the B.P. apparatus as the time to achieve 50% solution in distilled water, discriminated more effectively between the tablet batches. Tablets made using polyvinylpyrrolidone and methylhydroxyethyl cellulose had dissolution half lives of 3.65 and 3.30 minutes respectively, whilst tablets incorporating stearic acid and starch mucilage exhibited respective values of greater than 200 minutes and 117 minutes. The bioavailabilities of the four tablet formulations were assessed on a double blind basis in four healthy males aged 18-30 with reference to an oral frusemide solution. The bioavailability of each formulation was determined by two different methods and it was found that polyvinylpyrrolidone and methylhydroxyethyl cellulose rendered frusemide equally bioavailable (71.7% and 71.6% respectively) whilst the starch mucilage formulation rendered frusemide 25% less bioavailable (54.10%). The poorest binding agent was stearic acid which decreased the bioavailability of frusemide by 50% (35.04%). The results indicate that the choice of binding agent can significantly affect the bioavailability of frusemide from tablets and that these bioavailability differences can best be detected in vitro by dissolution rate measurements.     

Effect of Particle Size and Excipients on the Dissolution Rate of Metronidazole from Solid Dosage Forms: II

Abstract

In-vitro dissolution tests were carried out with tablets prepared from different particle size ranges of metronidazole. Influence of tablet binding agents (Methylcellulose, polyvinyl pyrrolidone - (PVP), potato starch and gelatin) on the drug release were investigated under similar conditions. Comprimates containing PVP and drug with particle size 1.75 μm (in lactose mixture) gave optimum results. These findings may open new ways of formulating a metronidazole tablet exhibiting improved drug - liberation, subsequently with a better bioavailability than the KUON^R-Tablet manufactured in Hungary.     

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.     

Natural rubber latex/potato starch nanocrystal nanocomposites: Correlation morphology/electrical properties

This paper discusses the preparation and characterization of nanocomposites obtained with potato starch nanocrystals, and their use as fillers in order to realize nanocomposites with a natural rubber latex matrix. The preparation of potato starch nanocrystals was done by hydrolysis of potato starch powder using sulfuric acid. The synthesized potato starch nanocrystal suspensions were mixed with natural rubber latex by latex stage mixing process using a magnetic stirrer. In this way, composites containing up to 20% w/w of fillers have been obtained. Morphological studies indicated a relatively uniform dispersion of starch nanocrystals in the nanocomposites until 15% w/w filler loading. Dielectric measurements confirm the existence of a threshold at a composition close to 15% w/w of filler at which the fillers become agglomerated.     

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 influence of starch swelling on the material properties of cooked potatoes

Cooked potatoes have a wide range of food applications, but the mechanism by which softening occurs on heating is not clearly understood. Heating potato parenchyma tissue results in two independent, concurrent events; weakening of the binding between cells and swelling of intra-cellular starch. Potato plants containing starches with a range of high amylose contents and reduced swelling properties were available. This provided the opportunity to separate cooking effects of inter-cellular pectin from swelling of intra-cellular starch. Their individual contribution to the separation of cells and the softening of cooked potato tissue was established by studying the influence of heat on the material properties of a range of starch-modified potatoes. For all potato lines studied, the strength of the heated tissue decreased markedly following 30 minutes at 80°C or 5 minutes at 100°C. Microscopy of the line in which there was minimal starch swelling, indicated that the cells of the cooked tissue principally contained fluid, in contrast to the controls in which the cells were filled with swollen starch on cooking. Since all the lines followed the same trend with regard to the thermal weakening of the tissue, we conclude that weakening of potato tissue on cooking is primarily controlled by thermal degradation of the middle lamella.     

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.     

Resistant starch as a carrier for oral colon-targeting drug matrix system

In this study, a novel tablet of protein drug matrix for colon targeting was developed using resistant starch as a carrier prepared by pre-gelatinization and cross-linking of starch. The effects of pre-gelatinization and cross-linking on the swelling and enzymatic degradation of maize starch as well as the release rate of drug from the matrix tablets were examined. Cross-linked pre-gelatinized maize starches were prepared by double modification of pre-gelatinization and cross-linked with POCl₃, and bovine serum albumin was used as a model drug. For in vitro drug release assays, the resistant starch matrix tablets were incubated in simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid, respectively. The content of resistant starch and swelling property of maize starch were increased by pre-gelatinization and cross-linking, which retarded its enzymatic degradation. Drug release studies have shown that the matrix tablets of cross-linked pre-gelatinized maize starch could delivery the drug to the colon. These results indicate that the resistant starch carrier prepared by pre-gelatinization and cross-linking can be used for a potential drug delivery carrier for colon-targeting drug matrix delivery system.     

Effects of Temperature,Humidity, and Aging on the Disintegration and Dissolution of Acetaminophen Tablets

Abstract

The effect of storage for 8 weeks at 40°C in moderate and high humidity on acetaminophen tablets prepared by the wet granulation method using povidone or pregelatinized starch as a binder was studies. Storage at 52% relative humidity produced an increase in hardness of acetaminophen tablets and storage at 94% relative humidity caused a decrease in hardness. In all cases tablets granulated with pregelatinized starch were less susceptible to change caused by humidity than tablets granulated with povidone. The disintegration of tablets containing starch or povidone was slowed as the humidity was increased. Tablets stored at 40 =C and 94 V. relative humidity showed a substantial slowing of dissolution, but there was little change of dissolution of tablets when aged at 40 -C / 52% relative humidity. In comparing starch and povidone as binders, acetaminophen tablets prepared with pregelatinized starch were less effected by high humidity than tablets prepared with povidone.     

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.     

裂解色谱对淀粉丙烯酰胺接枝物的研究

本文用裂解色谱法对淀粉丙烯酰胺接枝共聚物进行裂解分析,从裂解谱图上能够得到淀粉和丙烯酰胺的特征裂解碎片峰,同时从接枝物中淀粉和丙烯酰胺特征碎片峰的面积可计算出淀粉或丙烯酰胺的相对比例。确定淀粉在接枝物中的分布,由接枝物的裂解色谱图还可得到峰面积和接枝率的关系图,从此关系图中可直观得到接枝物的接枝率,对于研究淀粉接枝共聚物的结构和性能有一定的参考意义。