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.     

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.     

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.     

A Comparison of Trehalose Dihydrate and Mannitol as Stabilizing Agents for Dicalcium Phosphate Dihydrate Based Tablets

This study investigated the possible utility of trehalose dihydrate (TD) as a tablet stabilizing agent. Acetylsalicylic acid was used as the model hydrolyzable drug and dicalcium phosphate dihydrate (DCPD) as the base excipient, because it is well documented that ASA/DCPD tablets are unstable during storage at low temperature and high relative humidity; DCPD is usually combined with mannitol in order to improve tablet stability.

Tablets comprising DCPD, 10% ASA, and 0%, 10%, or 20% w/w of TD were prepared by direct compression and stored at 35°C and 82.9% relative humidity for 6 months. Additionally, control tablets with DCPD and ASA, only, or with DCPD, ASA and 20% mannitol, were also evaluated. At predetermined time intervals, formulations were tested for drug content, mechanical, microstructural, and drug dissolution properties. Additionally, thermal analyses and ASA solution stability studies were carried out. Results reveal that both TD and mannitol significantly reduce degradation of ASA included in DCPD-based tablets, but neither effectively protects against the marked decline in tablet mechanical properties on aging. The ASA stabilization effects of TD and mannitol were also observed in solution, indicating an interaction between these sugars and ASA.     

A comparison of trehalose dihydrate and mannitol as stabilizing agents for dicalcium phosphate dihydrate based tablets

This study investigated the possible utility of trehalose dihydrate (TD) as a tablet stabilizing agent. Acetylsalicylic acid was used as the model hydrolyzable drug and dicalcium phosphate dihydrate (DCPD) as the base excipient, because it is well documented that ASA/DCPD tablets are unstable during storage at low temperature and high relative humidity; DCPD is usually combined with mannitol in order to improve tablet stability. Tablets comprising DCPD, 10% ASA, and 0%, 10%, or 20% w/w of TD were prepared by direct compression and stored at 35 degrees C and 82.9% relative humidity for 6 months. Additionally, control tablets with DCPD and ASA, only, or with DCPD, ASA and 20% mannitol, were also evaluated. At predetermined time intervals, formulations were tested for drug content, mechanical, microstructural, and drug dissolution properties. Additionally, thermal analyses and ASA solution stability studies were carried out. Results reveal that both TD and mannitol significantly reduce degradation of ASA included in DCPD-based tablets, but neither effectively protects against the marked decline in tablet mechanical properties on aging. The ASA stabilization effects of TD and mannitol were also observed in solution, indicating an interaction between these sugars and ASA.     

Effect of packaging and storage on the stability of carbamazepine tablets

The effect of packaging and storage on carbamazepine (CBZ) tablets was examined using Tegretol® and Tegral, dispensed in strip seals, and Finlepsin®, dispensed in bottles. Tegretol and Tegral tablets were stored in their original strips at 40°C, 50°C, and 60°C for 6 months, 3 months, and 1 month, respectively, at 75% relative humidity (RH). Also, tablets were removed from their strips, placed in bottles, and exposed daily to 97% RH at 40°C for 5 min for 30 days. Finlepsin tablets were exposed to 97% RH at 25°C or 40°C for 1 month by removing bottle caps daily for 5 min. Dissolution was used to assess in vitro tablet performance, and high-performance liquid chromatography (HPLC) was used to evaluate the chemical stability of CBZ. Results show that Tegretol tablets were not affected by the tested stress conditions. Tegral tablets, stored in their strips at 50°C or 60°C and 75% RH, showed increased disintegration and dissolution. The effect of 40°C/75% RH for 6 months was similar to 1-month storage at 40°C/97% RH; the tablets hardened and dissolved less than fresh Tegral tablets. Removal of Tegral tablets from their original strips resulted in only 7% dissolved in 60 min. For Finlepsin, the effect of 97% RH at 40°C was more profound than 97% RH at 25°C, but both conditions caused a decrease in dissolution, the extent of which was dependent on tablet position in the bottle. Stressed CBZ tablets, however, showed no change in the chemical stability of CBZ under all tested conditions.     

Effect of Crystallization of Theophylline on Physical Properties of Tablets

Tablets containing anhydrous theophylline, a hygroscopic material such as magnesium chloride or potassium acetate, and other constituents were stored for 4 and 12 weeks under 90% relative humidity at 37°C. During storage, whisker-like crystals appeared on the surface of the tablets. The crystals were observed under a scanning electron microscope. Changes were found in the physical properties of these tablets: crushing strength, friability, disintegration time and dissolution rate.     

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

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 Crystallization of Theophylline on Physical Properties of Tablets

Abstract

Tablets containing anhydrous theophylline, a hygroscopic material such as magnesium chloride or potassium acetate, and other constituents were stored for 4 and 12 weeks under 90% relative humidity at 37°C. During storage, whisker-like crystals appeared on the surface of the tablets. The crystals were observed under a scanning electron microscope. Changes were found in the physical properties of these tablets: crushing strength, friability, disintegration time and dissolution rate.     

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 Storage on the Properties of Acetylsalicylic acid Tablets Coated with Aqueous Hydroxypropyl Methyl-Cellulose Dispersion

The objective of this study was to investigate whether the properties of acetylsalicylic acid tablets coated with aqueous hydroxypropyl methylcellulose dispersion using glycerol or polyethylene glycol 6000 as plasticizer change during storage at 25° or 40°C. Titanium dioxide was used as pigment. The tablets were coated in a fluid bed apparatus. The disintegration time and the release of acetylsalicylic acid during two hours were determined for both uncoated and coated tablets immediately after their preparation and after different storage periods.

When the tablets were stored at room temperature (25°C) the coat protected the core efficiently against changes in the measured parameters as compared with uncoated tablets. However, at higher temperature (40°C) some unfavorable phenomena occurred in the coat and after storage of 48 months, the disintegration time was longer and the dissolution of acetylsalicylic acid slower than from uncoated tablets. Polyethylene glycol was found to be a better protecting agent than glycerol.     

Effect of Storage on the Properties of Acetylsalicylic acid Tablets Coated with Aqueous Hydroxypropyl Methyl-Cellulose Dispersion

Abstract

The objective of this study was to investigate whether the properties of acetylsalicylic acid tablets coated with aqueous hydroxypropyl methylcellulose dispersion using glycerol or polyethylene glycol 6000 as plasticizer change during storage at 25° or 40°C. Titanium dioxide was used as pigment. The tablets were coated in a fluid bed apparatus. The disintegration time and the release of acetylsalicylic acid during two hours were determined for both uncoated and coated tablets immediately after their preparation and after different storage periods.

When the tablets were stored at room temperature (25°C) the coat protected the core efficiently against changes in the measured parameters as compared with uncoated tablets. However, at higher temperature (40°C) some unfavorable phenomena occurred in the coat and after storage of 48 months, the disintegration time was longer and the dissolution of acetylsalicylic acid slower than from uncoated tablets. Polyethylene glycol was found to be a better protecting agent than glycerol.     

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     

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 Physical Stability of Tablets Coated using an Aqueous Dispersion of Ethylcellulose

Films formed from an aqueous dispersion of ethylcellulose mixed with hydroxypropylmethylcellulose were deposited onto sodium bicarbonate, microcrystalline cellulose, and acetylsalicylic acid (ASA) tablets. Upon storage at elevated temperatures and relative humidity, no changes in disintegration times were observed with the sodium bicarbonate tablets or with tablets containing microcrystalline cellulose. Marked increases were observed in disintegration times with the ASA tablets, these increases being dependent on both temperature and relative humidity. Examination of films by scanning electron microscopy indicated that coalescence of particles within the films had occurred in those samples where increases in disintegration times were observed.     

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.     

The Stability of Theophylline Tablets with a Hydroxypropylcellulose Matrix

The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20°C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).     

The stability of theophylline tablets with a hydroxypropylcellulose matrix

The behavior of 40:60 anhydrous theophylline/hydroxypropylcellulose (HPC) direct compression tablets obtained using a variety of hydroxypropylcelluloses with low or medium-high degrees of substitution (L-HPCs and HPCs, respectively) was determined immediately following their preparation and after storage for 6 months at 20°C and a relative humidity (RH) of either 70.4% or 93.9%. The lower relative humidity did not bring about hydration of the active principle in any formulation, but the higher relative humidity totally hydrated the drug in all except one L-HPC formulation, in which hydration remained incomplete. Both relative humidities caused significant tablet swelling, with L-HPC formulations being more affected than HPC formulations. Drug release was slowed by hydration of the active principle, but accelerated with tablet swelling. The lower relative humidity caused significant alteration of drug release characteristics in only two L-HPC formulations, release from which was accelerated, while the higher relative humidities only failed to cause such alterations in two HPC formulations, with release from all except one of the others slowed (in the exceptional formulation, which exhibited incompletely hydrated theophylline and the greatest swelling of all, release was accelerated).     

The Effect of Environmental Moisture and Temperature on the Physical Stability of Effervescent Tablets in Foil Laminate Packages Containing Minute Imperfections

The effect of environmental moisture on the physical stability of effervescent tablets in foil laminate packages containing microscopic imperfections (openings) was examined. Packaged tablets were stored at different relative humidity (RH) and temperature conditions and evaluated for physical stability at predetermined time intervals. Physical stability was assessed by noting if the tablet components reacted prematurely to yield soft tablets during storage. A penetrating dye solution test was used to determine if the foil packages contained imperfections which might allow transmission of moisture. The results of the investigation indicated that absolute moisture integrity of the foil package is required for product stability.     

Comparative Aging Studies of Tablets Made with Diabasic Calcium Phosphate Dihydrate and Spray Dried Lactose

There are relatively few published reports on the aging of tablets (1-4) and thus, as an extension of previously published work, the aging of compressed tablets (prepared using either dibasic calcium phosphate dihydrate or spray^A dried lactose as matrix) has been investigated over a sixty-five day period. All tablets contained 6% amaranth as a dye tracer, 0.5% magnesium stearate as lubricant and 2.5% sodium alginate as disintegrant. Tablets were prepared by direct compression on a single punch press and stored under three sets of stress conditions: (a) 25°C, 45% relative humidity (RH); (b) 35°C, 60% RH; (c) 45°C, 75% RH.

Tablets were evaluated by appearance (visual and photography); weigh; size; hardness (Erweka); disintegration time (U.S.P.); and dissolution (U.S.P.). A transient mottling phenomenon was evident in both systems under accelerated conditions. Significant weight variations were observed at all temperatures for the dibasic calcium phosphate dihydrate system, while lactose tablets showed only slight changes in weight. Under accelerated storage conditions, hardness appears to be related to disintegration times and dissolution rates with either system. However, it is not a reliable tool at room temperature. In addition, results at accelerated conditions do not appear to be directly related to those obtained at room temperature.