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 on the physical characteristics of ranitidine hydrochloride tablets prepared by different binders and techniques

Abstract

The effect of moisture on the physical properties of ranitidine hydrochloride tablets prepared by direct-compression and by wet-granulation method using PVP or EC as binders was studied. Tablets adsorped moisture at 50 and 75 % RH (relative humidity) but lost moisture at 30% RH. Except storage at 75% RH, however, tablet volumes did not change significantly during the test period. Moisture sorption caused a decrease in strength of tablets except low humidity (30% RH). Also, the disintegration time of tablets showed a decrease at all conditions except 30% RH. Furthermore, generally dissolution profiles of tablets prepared by direct-compression and by ethyl cellulose remained unchanged. Changes in the binder type in the tablet formulations changed the water uptake properties and also the physical properties of tablets. Directly-compressed tablets were much susceptible to change caused by humidity than tablets prepared by wet-granulation.     

Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Abstract

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

The Effect of Compaction Force and Type of Pregelatinized Starch on the Dissolution of Acetaminophen

Abstract

The influence of four pregelatinized starches—National® 1551, Lycatabps, Pregeflo®M, and Starch 1500®—as binders, on the dissolution of acetaminophen was evaluated in a model wet-granulated system. Systems containing 82% acetaminophen were prepared under the same processing conditions and compacted to three target tablet thicknesses. The dissolution performance was assessed using a point estimate of percent dissolved at 30 min (%T₃₀) as well as dissolution eflciency through 30 min (DE₃₀). All four binders evaluated meet USP requirements for purity. National 1551, Lycatab PGS, and Starch 1500 were not affected by compaction force in terms of dissolution performance. Differences were observed between the fully pregelatinized systems of National 1551 and Lycatab PGS, in comparison to the partially pregelatinized system, Starch 1500. The Pregeflo M starch produced a system with delayed drug dissolution and was influenced by compaction force.     

The effect of moisture on the physical characteristics of ranitidine hydrochloride tablets prepared by different binders and techniques

The effect of moisture on the physical properties of ranitidine hydrochloride tablets prepared by direct-compression and by wet-granulation method using PVP or EC as binders was studied. Tablets adsorped moisture at 50 and 75 % RH (relative humidity) but lost moisture at 30% RH. Except storage at 75% RH, however, tablet volumes did not change significantly during the test period. Moisture sorption caused a decrease in strength of tablets except low humidity (30% RH). Also, the disintegration time of tablets showed a decrease at all conditions except 30% RH. Furthermore, generally dissolution profiles of tablets prepared by direct-compression and by ethyl cellulose remained unchanged. Changes in the binder type in the tablet formulations changed the water uptake properties and also the physical properties of tablets. Directly-compressed tablets were much susceptible to change caused by humidity than tablets prepared by wet-granulation.     

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.     

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     

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.     

Fluidized-Bed agglomeration of acetaminophen; direct compression of tablets and physiologic availability

A novel process was developed for manufacturing acetaminophen in a free-flowing, directly compressible agglomerated form, involving spray agglomeration of acetaminophen powder with polyvinylpyrrolidone (PVP) in isopropyl alcohol as a bonding agent using a fluidized-bed granulator. Agglomerates prepared with 5% PVP yielded a free-flowing and compressible material. Upon lubrication with 0.5% magnesium stearate, the material was found to be directly compressible into tablets. To improve dissolution and tableting properties, the agglomerates were compressed into tablets after blending with varying weight ratios of microcrystalline cellulose/pregelatinized starch as a filler/disintegrant combination. The final stable tablet formulation consisted of agglomerates equivalent to 325 mg of acetaminophen, 2.1 mg of magnesium stearate, and the filler/disintegrant in a weight ratio of 70:30 to yield a tablet weight of 425 mg. Physical properties and dissolution profile of these tablets were comparable to those of a commercial acetaminophen tablet. Physiologic availability calculated using the urinary excretion method indicated half-lives of 2.0, 2.1, and 2.2 hours for control (acetaminophen powder), experimental tablet, and a marketed product, respectively.     

The Effect of Compaction Force and Type of Pregelatinized Starch on the Dissolution of Acetaminophen

The influence of four pregelatinized starches—National® 1551, Lycatabps, Pregeflo®M, and Starch 1500®—as binders, on the dissolution of acetaminophen was evaluated in a model wet-granulated system. Systems containing 82% acetaminophen were prepared under the same processing conditions and compacted to three target tablet thicknesses. The dissolution performance was assessed using a point estimate of percent dissolved at 30 min (%T₃₀) as well as dissolution eflciency through 30 min (DE₃₀). All four binders evaluated meet USP requirements for purity. National 1551, Lycatab PGS, and Starch 1500 were not affected by compaction force in terms of dissolution performance. Differences were observed between the fully pregelatinized systems of National 1551 and Lycatab PGS, in comparison to the partially pregelatinized system, Starch 1500. The Pregeflo M starch produced a system with delayed drug dissolution and was influenced by compaction force.     

Oral disintegrating patient-tailored tablets of warfarin sodium produced by 3D printing

Abstract

Individualized medicine is a new direction in the field of modern pharmacy. In this study, we assessed the feasibility and accuracy of 3D printing techniques for the preparation of individualized doses of mouth-disintegrating tablets of warfarin. Warfarin sodium, D-sucrose, pregelatinized starch, povidone K30, microcrystalline cellulose, and silicon dioxide (at a ratio of 1:42.45:46.15:5.1:4.9:0.4) were mixed and used as the printing powder in the 3D printer; preset parameters were used. The dosage of the tablet was controlled by the number of printing layers. The content, dose uniformity, dose accuracy, hardness, friability, disintegration time, dissolution, and the microstructural and overall appearance were determined to evaluate the printed tablets. For the doses of 3, 2, and 1?mg that were produced in the experiment, the disintegration times were 50.0?±?5.2, 35.7?±?4.3, and 11.0?±?2.2?s, respectively, and the relative errors of the dose were ?2.33, ?1.50, and 0%, respectively. The other indicators were consistent with the preparation requirements of pharmaceutical tablets. It is possible to prepare tablets with excellent properties and controlled drug doses by using 3D printing techniques. This technology will be an important means to achieve individualized medicine.     

Directly Compressible Acetaminophen Compositions Prepared by Fluidized-Bed Granulation

Polyvinylpyrrolidone (PVP) in aqueous solution was used as a binding agent in a fluidized-bed system to agglomerate acetaminophen powder into directly compressible granules. It was found that a minimal amount of 5% w/w PVP in a concentration of 7.5% w/v or less was needed to produce granules with an acceptable flow and the corresponding tablets having enough hardness without capping. There was a strong correlation between the time for 80% dissolved (T₈₀) and the logarithm of granule volume-surface mean diameter. A directly compressible acetaminophen composition to manufacture tablets having a T₈₀ value less than 30 min can be prepared simply by adding an appropriate amount of disintegrant (crospovidone, sodium starch glycolate, or pregelatinized starch) to the agglomerated granules.     

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.     

Effect of Moisture on the Physical and Chemical Stability of Granulations and Tablets of the Angiotensin Converting Enzyme Inhibitor,Enalapril Maleate

Abstract

Granulations and tablets of enalapril maleate in a lactose matrix were stored in open petri dishes at a range of relative humidities and respective moisture uptakes measured, Extrapolation of the moisture uptake rates measured at the exaggerated humidities yielded a critical humidity, i.e. humidity where the moisture uptake rate is zero and, therefore, least detrimental to the product.

Enalapril maleate was reasonably stable at the storage conditions. The hardness of the tablets decreased at all humidities except when stored with silica-gel. The disintegration times were unaffected except at very high humidities. The dissolution profiles of the tablets remained unchanged.     

Effect of Crospovidone on the Physical Properties of Acetaminophen Tablets

Abstract

Acetaminophen tablets containing minimum amount of excipients and varying amounts of cross linked polyvinyl pyrrolidone were prepared under accurately controlled conditions of compression speed and pressure. The disintegration time, dissolution rate, crushing force, friability as well as effect of temperature and humidity on these parameters during storage were determined. Increasing proportions of the cross linked polymer (1-10%) did not influence crushing force or friability but significantly decreased disintegration and dissolution time. Satishctory tablets with desired properties were obtained by incorporation of optimum quantity of crospovidone. Storage of acetaminophen tablets at room temperature and humidity for a period of 4 weeks did not alter any of the physical properties tested weekly. However the combined effect of elevated temperature and humidity on tablet properties, especially on the dissolution time was significant. The influence of incorporation of equal amounts of crospovidone intragranularly and intra-plus extragranularly on the properties of granules and tablets were also evaluated with scaled-up formulations.     

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     

Crosslinked Starch as Sustained Release Agent

Different types of crosslinked starches and pregelatinized-crosslinked starches were evaluated for their use as hydrophilic matrices. Some fundamental properties of these chemically modified starches, e.g. granule swelling power and viscosity of the dispersion in function of pH and ionic strength, were studied. Dissolution tests and the rate and amount of water uptake were evaluated on tablets containing theophylline and modified starch (40/60 w/w), compressed on an instrumented tablet press at three different pressures (50,200 and 300 MPa.). Theophylline releasing profiles were determined using the paddle system at a rotational speed of 50 rpm Water, simulated gastric fluid, and simulated intestinal fluid were used as dissolution media. Crosslinked starches showed a poor swelling power and dispersion viscosity in comparison to pregelatinized starch and pregelatinized-crosslinked starches. The pregelatinized-crosslinked starches developed less swelling power than the pregelatinized starch, but they showed higher dispersion viscosity than the pregelatinized starch. The viscosity of all starch dispersions was not affected by ionic strength. An alkaline pH dramatically increased the dispersion viscosity of pregelatinized starch and pregelatinized-crosslinked starches. Drug dissolution rate was lower for tablets containing pregelatinized starch than for tablets containing pregelatinized-crosslinked starches. This phenomenon can be related to the rate and amount of water uptake. The dissolution rate seemed not to be influenced by the compression force nor by the composition of the dissolution media. The results indicate that crosslinked starches, either pregelatinized or not, are not suitable as sustained release agents.     

Development and In-Vitro Characterization of Sustained-Release Acetaminophen Tablets

Abstract

The objective of this study was to evaluate powdered lipids as both granulating agents and retardants in formulated sustained-release acetaminophen tablets. Castor Wax or Durkee 07 powders were premixed with acetaminophen and granulated with boiling water. After cooling, the mass was screened to obtain a 10/20 mesh fraction which was used for tablet production and evaluation. Friability, hardness, dissolution and compression profiles were monitored. As lipid content increased from 5-15% w/w, friability and hardness also increased. Dissolution showed an inverse relationship between level of lipid and release rate. Compression profiles demonstrated good transmission when Castor Wax was employed. This study demonstrated that a high milligram potency tablet could be fabricated with low levels of lipid, to retard drug release, without significantly increasing tablet weight and size.     

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.