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.     

Evaluation of Fast Disintegrants in Terfenadine Tablets Containing a Gas-Evolving Disintegrant

Abstract

Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaC0₃, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone < Ac-Di-Sol < Primojel < low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.     

The Swelling & Water Uptake of Tablets III: Moisture Sorption Behavior of Tablet Disintegrants

Water vapor sorption properties and the thermal behavior of four disintegrants including microcrystalline cellulose (Avicel PH102), croscarmellose sodium (Ac-di-sol), corn starch, and sodium starch glycolate (Primojel), were studied. They all exhibited type II-like isotherm. The apparent monolayer sorption for each of disintegrants was found to be significantly greater than the specific surface obtained from nitrogen adsorption. It is proposed that water molecules interact with specific sites on the disintegrant glassy polymer. Water tends to stay as a condensed phase on the polymer, rather than to diffuse into the bulk. Water plasticization caused glass transition temperature (T_g) of all disintegrant polymers to decrease. It facilitated a change from glass to the rubber state. Because the sorption sites were in the glassy state, the change from glass to rubber, which in turn kinetically reduced the available sites, would reflect the sorption capacity of a disintegrant polymer. In addition, the difficulty in freezing a disintegrant's sorbed water was encountered.     

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.     

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

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.     

Dissolution Kinetics Evaluation of Controlled-Release Tablets Containing Propranolol Hydrochloride

In the present research, controlled-release propranolol hydrochloride tablets were prepared for twice-daily administration, allowing more uniform plasmatic levels of the drug. Pharmaceutical formulations were prepared with hydrophobic Eudragit® RSPO. The physical properties of the tablets were determined. Dissolution tests were performed in capsules containing the raw material using the following dissolution media: (A) distilled water, (B) simulated gastric juice without enzymes, and (C) simulated enteric juice without enzymes. A dissolution test was also performed for simulated samples (tablets) using distilled water as the dissolution medium.     

The Swelling of Core Tablets During Aqueous Coating I: A Simple Model Describing Extent of Swelling and Water Penetration for Insoluble Tablets Containing a Superdisintegrant

Abstract

A simple mathematical model was established to describe changes of tablet thickness due to swelling and water penetration during aqueous coating process. The model was illustrated by a simple linear equation, i.e.; D = -(α/(l+ε))l₁,+(α/(l+ε))l₀; where D, l₀,1₁, α and ε are the depth of water penetrating into tablets, initial tablet thickness, the remaining dried core tablet thickness, swelling and porosity parameters, respectively. The data from dicalcium phosphate dihydrate(Ditab) tablets containing a super-disintegrant may be fitted into the model showing significant statistical correlation. The model was valid for describing the extent of tablet swelling and water penetration during aqueous coating.     

Effect of Aging on the Bioavailability of Nitrdfurantoin Tablets Containing Carbopol 934

Abstract

This article reports a study of two nitrofurantoin tablet formulations differing in the percentage of Carbopol 934 used as binder. The tablets of both formulations each contained 50 mg of nitrofurantoin. Those of formulation A contained 0.625 mg of Carbopol 934, and those of formulation B 1.25 mg. When freshly prepared, tablets of both formulations were bioequivalent to capsules containing 50 mg of nitrofurantoin, but a year's storage at 40°C and 60% relative humidity caused a significant decrease in the bioavailability of nitrofurantoin from formulation B, whereas formulation A was still bioequivalent to capsules. USP XXI Ed. Method II successfully reflected the observed variations in bioavailability, but not Method I.     

Effect of Aging on the Bioavailability of Nitrdfurantoin Tablets Containing Carbopol 934

This article reports a study of two nitrofurantoin tablet formulations differing in the percentage of Carbopol 934 used as binder. The tablets of both formulations each contained 50 mg of nitrofurantoin. Those of formulation A contained 0.625 mg of Carbopol 934, and those of formulation B 1.25 mg. When freshly prepared, tablets of both formulations were bioequivalent to capsules containing 50 mg of nitrofurantoin, but a year's storage at 40°C and 60% relative humidity caused a significant decrease in the bioavailability of nitrofurantoin from formulation B, whereas formulation A was still bioequivalent to capsules. USP XXI Ed. Method II successfully reflected the observed variations in bioavailability, but not Method I.     

脱脂紫茎泽兰细度对水凝胶溶胀动力学的影响

以不同细度粉末状脱脂紫茎泽兰(EA)为原料,研究在相同的接枝共聚条件下所得的水凝胶的溶胀行为。实验表明:在45～75μm范围内,随着原料颗粒细度的降低,所得相应凝胶的溶胀速率和溶胀度均增大,水分子在凝胶中的扩散行为可用non-Fickian扩散来描述;在30～45μm时所得凝胶的溶胀过程符合Fickian扩散规律。通过Beren-Hopfenberg微分方程,计算得到凝胶吸液值大于60%时的溶胀扩散常数。利用Arrhenius公式计算得到相应的活化能均在69.0～89.0kJ·mol-1范畴内,且随原料颗粒细度的减小,凝胶Ⅱ-1-Ⅱ-4的Ea值呈下降趋势;而Ⅱ-5的活化能略高于Ⅱ-4,但仍小于其他凝胶的Ea值。     

Effect of Drug Solubility in Wet Granulation Fluids on the Dissolution Rates of the Resulting Tablets

One factor in wet granulation processes which affects dissolution rates of the final tablets is shown to be the solubility of the drug substance in the granulating liquid. The relationship is not a direct correlation and a feasible explanation is offered.     

Tie Effect of Disintegrants and Processing on the Bioavailability of Frusemide from Compressed Tabllts

Abstract

Batches of frusemide tablets were produced using Explotab, polyplasdone XL, Amberlite IRP88, maize atarch, and Elcesan P100 as disintegrants. Bioavailability atudies were carried out on a double blind basis.

The bioavailability differences between formulations was shown to be significant. Explotab rendered the fruseulide far more bioevailable than the other four disintegrants.     

Tie Effect of Disintegrants and Processing on the Bioavailability of Frusemide from Compressed Tabllts

Batches of frusemide tablets were produced using Explotab, polyplasdone XL, Amberlite IRP88, maize atarch, and Elcesan P100 as disintegrants. Bioavailability atudies were carried out on a double blind basis.

The bioavailability differences between formulations was shown to be significant. Explotab rendered the fruseulide far more bioevailable than the other four disintegrants.     

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.     

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

Abstract

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.     

The Effect of the Wet Granulation Process on Drug Dissolution

Abstract

Wet granulation can be an important processing step for pharmaceutical solid dosage forms. In this investigation emphasis was directed towards the influence of a “simple” wet granulation process on drug release from granules and their resulting tablets. Direct compression blends of the same materials were used as controls. Binary mixtures containing a 5% level of either theophylline, hydrochlorothiazide or chlorpheniramine maleate in microcrystalline cellulose or lactose were granulated with water. Experimentally, the powders were dry blended in a planetary mixer, wet granulated, and subsequently wet milled and dried. No dry milling step was included. Granule characterization consisted of particle size, density, porosity, compression and dissolution testing. Dissolution results varied with the drug, as expected, and dissolution at 10 minutes ranged from 35 to 95 % release. In general, however, the results indicate that dissolution from granules and the corresponding direct compression blend are similar. Although differences in compressibility were observed in the systems studied, granulation was not found to be detrimental to drug release.     

The Contributions of Erosion,Swelling, and Porosity to Theophylline Release Kinetics From Cissus populnea Polymer Matrices

The variable factors of erosion rate, swelling rate, and porosity were used in studying the release patterns of theophylline from our Cissus populnea polymer (CPP) matrices under the different factor combinations given by a simple 2ⁿ factorial experimental design. The zero-order slopes and correlation coefficients representing release rate and linearity, respectively, as obtained from both the nonsteady state and steady state were statistically treated. It appears that the nonsteady-state analysis is more suitable for studying the effects of individual factors, while the steady-state analysis appears more suitable for studying interaction effects of the factors. The study also showed that erosion is the main mechanism by which theophylline is released from the matrices, while swelling is responsible for maintaining linearity in the zero-order release curves. A careful examination of the statistical results shows some functional relationships between the factors, which should be considered in designing more detailed factorial experiments to enable the establishment of equation models for predicting the release profile of theophylline from our CPP matrices under any given dissolution condition.     

Effect of Tableting Pressure and Geometrical Factor of Tablet on Dehydration Kinetics of Theophyline Monohydrate Tablets

The effect of compression pressure and geometrical factors (thickness and diameter) of tablet on the dehydration kinetics of theophylline monohydrate tablets was studied using an infrared water-content measuring instrument. The dehydration rate of 2 cm diameter tablets decreased with increase in tabletting pressure. The dehydration rates of tablets also depended on tablet shape. The 2 cm diameter tablets (thin tablets) dehydrated faster than 1 cm diameter tablets (thick tablets). Dehydration of the powder bed (loosely packed tablets) and 2 cm tablets compressed at 49 MPa followed the two-dimensional phase boundary equation, and that of 2 cm diameter tablets compressed at 98 MPa and 196 MPa (thin tablets) followed the three-dimensional phase boundary equation. Dehydration of 1 cm diameter tablets compressed at 98 MPa (thick tablets) followed the one-dimensional diffusion equation. It seems that the dehydration of the tablet was controlled by the porosity and the surface area of the tablet. Therefore, tablet thickness and tabletting pressure are important factors affecting the dehydration mechanism.     

Effect of Tableting Pressure and Geometrical Factor of Tablet on Dehydration Kinetics of Theophyline Monohydrate Tablets

Abstract

The effect of compression pressure and geometrical factors (thickness and diameter) of tablet on the dehydration kinetics of theophylline monohydrate tablets was studied using an infrared water-content measuring instrument. The dehydration rate of 2 cm diameter tablets decreased with increase in tabletting pressure. The dehydration rates of tablets also depended on tablet shape. The 2 cm diameter tablets (thin tablets) dehydrated faster than 1 cm diameter tablets (thick tablets). Dehydration of the powder bed (loosely packed tablets) and 2 cm tablets compressed at 49 MPa followed the two-dimensional phase boundary equation, and that of 2 cm diameter tablets compressed at 98 MPa and 196 MPa (thin tablets) followed the three-dimensional phase boundary equation. Dehydration of 1 cm diameter tablets compressed at 98 MPa (thick tablets) followed the one-dimensional diffusion equation. It seems that the dehydration of the tablet was controlled by the porosity and the surface area of the tablet. Therefore, tablet thickness and tabletting pressure are important factors affecting the dehydration mechanism.     

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.