Storage Related Physico-Chemical Changes in Aspirin and Phenylbutazone Tablets Compressed With Different Initial Moisture Content

Abstract

The storage conditions as well as the compressional conditions of the aged tablets were found to have significant effect on their physico-chemical properties. In this study the changes in tablet weight, thickness, hardness, disintegration, drug release and drug content were evaluated for aspirin and phenylbutazone (pbz) tablets made with microcrystalline cellulose (MCC) and lactose bases. Tablets were made with different initial moisture content and stored at 40°C/90% relative humidity (R.H.). Tablet thickness was found, in general, to increase with storage, this increase was more prominent with aspirin. The increase in thickness was always accompanied with a decrease in hardness. There was a marked increase in disintegration time and decrease in dissolution rate of phenylbutazone tablets. This was more significant for the lactose based tablets, while, for aspirin tablets there was a negligible increase in both dissolution rate and the disintegration time. The present study indicated that incorporation of drugs in tablet bases has resulted in a different response towards storage     

Effect of Storage Conditions on the Hardness,Disintegration and Drug Release from Some Tablet Bases

Abstract

The effect of storage at relatively high temperature and humidity on tablets prepared from different bases was studied for up to eight weeks. Drug release from tablets was followed by measuring the concentration of a marker (amaranth) in the dissolution medium. Lactose and mannitol based tablets showed an increase in hardness and disintegration time, and a decrease in the initial rate of drug release. Sorbitcl based tablets, stored under 50°C/50% relative humidity (R.H.), showed a decrease in hardness and slower disintegration and dissolution. When stored under 40°C/90% R.H., the tablets were completely deformed within three days. Tricalcium phosphate and cellulose-based tablets did not show any storage related changes in hardness, disintegration or drug release.     

Effect of Storage Conditions on the Hardness, Disintegration and Drug Release from Some Tablet Bases

The effect of storage at relatively high temperature and humidity on tablets prepared from different bases was studied for up to eight weeks. Drug release from tablets was followed by measuring the concentration of a marker (amaranth) in the dissolution medium. Lactose and mannitol based tablets showed an increase in hardness and disintegration time, and a decrease in the initial rate of drug release. Sorbitcl based tablets, stored under 50°C/50% relative humidity (R.H.), showed a decrease in hardness and slower disintegration and dissolution. When stored under 40°C/90% R.H., the tablets were completely deformed within three days. Tricalcium phosphate and cellulose-based tablets did not show any storage related changes in hardness, disintegration or drug release.     

The Effect of Moisture Sorption and Desorption on Furosemide Tablet Properties

Abstract

The effect of moisture sorption and desorption on the physical characteristics of furosemide tablet was studied at moderately elevated temperatures and different relative humidity conditions over 20 days. The rate of moisture sorption and desorption was founud to follow first order kifietics within first hours. Except ambient conditions (RT/Amb.RH), moisture sorption caused a decrease in hardness values of furosemide tablets. Also the disintegration times of hydrated tablets showed a remarkeable decrease. Changes in hardness and disintegration time were dependent on the amount of water sorbed into the tablets. These significant changes occured during the first days of the test and then became invariant. The variations in hardness and disintegration times of tablets were irreversible as demonstrated by desorption experiments.

Furthermore, except storage at high temperature and high relative humidity dissolution parameters of tablets were less affected by moisture sorption and desorption.     

Moisture, Hardness, Disintegration and Dissolution Interrelationships in Compressed Tablets Prepared by the Wet Granulation Process

Interrelationships among moisture, hardness, disintegration and dissolution in compressed tablets were studied by compressing tablets from granulations prepared by the wet granulation process containing low moisture levels. Hardness, disintegration and dissolution of these tablets did not change on exposure to ambient room conditions. After equilibration under high humidities, a decrease in tablet hardness occurred which depended linearly on tablet hardnesses at the time of compression. After overnight exposure to ambient room conditions, the softened tablets increased in hardness and this increase greatly exceeded the initial hardnesses. The magnitude of hardness increase was independent of the hardnesses at the time of compression. Increased tablet hardnesses resulted in an increase in the disintegration time, although in vitro dissolution of the drug remained unaffected. The results suggest that moisture gain and subsequent loss on storage under varying humidity conditions could account for major increases in hardness of compressed tablets in storage.     

The Effect of Low- and High-Humidity Aging on the Hardness, Disintegration Time and Dissolution Rate of Tribasic Calcium Phosphate-Based Tablets

The effect of low- and high-humidity aging on hardness, disintegration time and dissolution rate of tribasic calcium phosphate-based tablets prepared at different initial moisture levels was studied. The tablet hardness, disintegration time and dissolution rate of the drug changed only slightly on aging under low humidity when the moisture contents at the time of compression were low. At higher initial moisture levels, the tablet disintegration time decreased and the dissolution rate increased, although no change in tablet hardness occurred on aging under low humidity. The tablets containing lower initial moisture decreased in hardness, increased in disintegration time and decreased in dissolution rate on aging under high humidity. A small or variable change in hardness, a large increase in the disintegration time and a large decrease in the dissolution rate was seen in tablets containing higher initial moisture contents on aging under high humidity. The results indicate that the moisture content of the tablet granulation at the time of compression and moisture gained during aging plays a significantly important role on hardness, disintegration time and dissolution rate of tribasic calcium phosphate-based tablets.     

Effects of Binders and Moisture Content on the Disintegration,Hardness and Friability of Paracetamol and Orphenadrine Citrate Tablets

Abstract

The effects of binders and moisture content on the disintegration time, friability and hardness of paracetamol and orphenadrine citrate tablets at different storage conditions were investigated. These parameters were determined after one, four and sixteen weeks of storage

The use of starch, ethocel or CMC Na as binders gave unsatisfactory tablets because of their high friability. Unacceptably high disintegration times were obtained, particularly at higher storage temperatures when PVP was used. Capping and yellow spotting observed in gelatin formulations makes this binder unsuitable for use. Methocel granulations yielded satisfactory tablets with acceptable disintegration time, hardness and friability and were unaffected by storage at different conditions of temperature and humidity     

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.     

Prelimnaky Evaluation of Cissus Root Gum as a Binder in Sodium Salicylate Tablet Formulations

Abstract

Cissus root gum was processed and evaluated as a binder in lactose-based tablets each containing 100 mg of sodium salicylate as the active ingredient. Acacia binder was used as basis for comparison. Tablet hardness, friability, disintegration time and dissolution rate were the parameters investigated. The cissus gum gave hard and non-friable tablets at 1 - 3% w/w concentration of the tablet formula. Tablets containing above 2% w/w of the cissus gum gave high disintegration time values and the pattern of dissolution of the incorporated drug suggests that the gum may be useful in prolonged release tablet formulations. No significant changes in the tablet properties was observed after storage at 30°C for 16 weeks.     

The Effect of Moisture Sorption and Desorption on Furosemide Tablet Properties

The effect of moisture sorption and desorption on the physical characteristics of furosemide tablet was studied at moderately elevated temperatures and different relative humidity conditions over 20 days. The rate of moisture sorption and desorption was founud to follow first order kifietics within first hours. Except ambient conditions (RT/Amb.RH), moisture sorption caused a decrease in hardness values of furosemide tablets. Also the disintegration times of hydrated tablets showed a remarkeable decrease. Changes in hardness and disintegration time were dependent on the amount of water sorbed into the tablets. These significant changes occured during the first days of the test and then became invariant. The variations in hardness and disintegration times of tablets were irreversible as demonstrated by desorption experiments.

Furthermore, except storage at high temperature and high relative humidity dissolution parameters of tablets were less affected by moisture sorption and desorption.     

Tablets containing drug-loaded polymeric nanocapsules: an innovative platform

The aim of the present work was to evaluate the feasibility to convert drug-loaded nanocapsule suspensions in a solid dosage form (tablets). Dexamethasone was used as a model drug due to its low aqueous solubility and fast drug release from conventional tablets. Granules containing dexamethasone-loaded nanocapsules were obtained by a wet granulation process using a dispersion of polyvinylpirrolidone/nanocapsules as a binder system. Granules were compressed in an eccentric compression machine (D-NC-T). A control formulation (tablets without nanocapsules) was also prepared (D-T). Tablets were characterized by means of mean weight, hardness, friability, diameter, thickness, disintegration time, drug content, morphological analysis by scanning electron microscopy (SEM), and in vitro drug release studies. D-NC-T showed adequate physicochemical characteristics according to the pharmacopeial requirements in terms of mean weight, hardness, friability, disintegration time and drug content. Intact nanocapsules in tablets were observed by SEM. In vitro drug release studies showed a slower release of dexamethasone from these tablets (D-NC-T) compared to the control formulation (D-T). Results showed that these tablets represent an interesting platform to the development of oral drug delivery systems containing polymeric nanocapsules.     

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.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Abstract

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.     

A Study of the Chemical and Physical Stability of Ascorbic Acid,Folic Acid,and Thiamine Hydrochloride Tablets Formulated with Emcompress Standard

Abstract

Tablets which were prepared from separate formulations of Emcompress Standard^R, a commercially available directly compressible granulation, with ascorbic acid, folic acid, and thiamine hydrochloride were subjected to accelerated aging conditions and studied for chemical stability and such physical parameters as hardness, friability, and disintegration time. Other physical factors which could affect the interpretation of the data, such as moisture content, particle size distribution, angle of repose, weight variation, and hardness were also studied using fresh samples.

Accelerated aging showed that the ascorbic acid formulation was chemically unstable; the tablets became soft, the frability increased markedly, and the disintegration time decreased. The folic acid formulation was chemically stable, but the tablets became soft, the friability increased, and disintegration time increased. The thiamine hydrochloride formulation was also chemically stable—the tablets became soft, the disintegration time decreased, and the friability increased.     

Effects of Binders and Moisture Content on the Disintegration, Hardness and Friability of Paracetamol and Orphenadrine Citrate Tablets

The effects of binders and moisture content on the disintegration time, friability and hardness of paracetamol and orphenadrine citrate tablets at different storage conditions were investigated. These parameters were determined after one, four and sixteen weeks of storage

The use of starch, ethocel or CMC Na as binders gave unsatisfactory tablets because of their high friability. Unacceptably high disintegration times were obtained, particularly at higher storage temperatures when PVP was used. Capping and yellow spotting observed in gelatin formulations makes this binder unsuitable for use. Methocel granulations yielded satisfactory tablets with acceptable disintegration time, hardness and friability and were unaffected by storage at different conditions of temperature and humidity     

Application of Fluidized Hot-Melt Granulation (FHMG) for the Preparation of Granules for Tableting; Properties of Granules and Tablets Prepared by FHMG

ABSTRACT

The objective of this study was to investigate the properties of granules and tablets prepared by a novel Fluidized Hot-Melt Granulation (FHMG) technique. Macrogol 6000 (polyethylene glycol 6000, PEG 6000), macrogol 20000 (polyethylene glycol 20000, PEG 20000), and glyceryl monostearate (GMS) were used as binders with different levels of viscosity and water solubility. The properties of both granules and tablets were compared with those obtained using the Standard Tablet Formulation (STF, lactose/corn starch/hydroxypropylcellulose/magnesium stearate: 66/30/3.5/0.5) for fluidized-bed granulation, which is widely used for wet granulation. To obtain suitable flowability as granules for tabletting, the content of the melting material should be approximately 10 w/w%. The rate of increase in the mean diameter of the granules during FHMG was affected by both the melting temperature and the viscosity of the melting material used in the granules. The compression properties of granules prepared by FHMG were also investigated, demonstrating that these granules had a high pressure transmittance. The hardness and the disintegration time of tablets obtained from granules prepared by FHMG were influenced by the properties of the melting material, such as its compaction behavior, solubility, and wettability. No significant differences of hardness were observed when compared to STF tablets. Tablets prepared from FHMG granules disintegrated within 15 min, whereas the STF tablets showed faster disintegration. It was also demonstrated that the hardness and disintegration time of tablets prepared from FHMG granules were not affected by the tablet porosity. Therefore, tablets with a constant quality may be obtainable under a wide range of compression forces. The results of this study suggested that FHMG is a useful method of preparing granules for tableting without using any solvents or water.     

Hydrate Related Dissolution Characteristics of Norfloxacin

Abstract

The effect of moisture and temperature on the physical and chemical stability of solid oral dosage forms of Norfloxacin was studied. The physical properties of the dosage form, i. e. breaking strength and disintegration time were not affected adversely. Dissolution characteristics of Norfloxacin tablets were found to be affected by humidity conditions. Tablets with poor dissolution characteristics were improved to satisfactory rates by exposure to 21–25°C/75% relative humidity. Exposure to lower humidities and higher temperatures adversely affected dissolution rates. Once favorable dissolution rates were attained, however, they remained unchanged in spite of dehydration of the tablets.     

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.     

Spray-Dried Rice Starch: Comparative Evaluation of Direct Compression Fillers

Spray-dried rice starch (SDRS), microcrystalline cellulose (MCC), lactose (L), pregelatinized starch (PS), and dibasic calcium phosphate (DCP) were studied for their flow behaviors and tableting properties. Both flow rate and percent compressibility values indicated that SDRS exhibited excellent flowability. The increase in magnesium stearate content reduced the hardness of MCC and SDRS tablets; however, general tablet properties were still acceptable while the PS tablets were unsatisfactory at high lubricant concentrations. The hardness of L or DCP tablets was not affected by the lubricant. The disintegration of L tablets was prolonged with the increased lubricant concentration while that of PS tablets seemed to be decreased due to softened tablets. The disintegration times of MCC and SDRS tablets seemed to be independent of the lubricant added. With respect to the dissolution, SDRS-based tablets offered fast and complete release of the drug regardless of its solubility. SDRS, L, and DCP exhibited comparable carrying capacity for ascorbic acid. The best dilution potential was obtained with MCC while the worst was obtained with PS.