Tablet Surface Area Research Articles

Effect of Dissolution Rate and Food on Oral Bioavailability of Bropirimine Tablets in Dogs

Three different tablet formulations of bropirimine were evaluated in an in vitro dissolution study. Further, the effect of dissolution rate of bropirimine and food on the bioavailability after oral administration of the tablets was investigated in dogs. A tablet formulation with lower bropirimine content percent and smaller tablet size showed faster in vitro dissolution rate due to the larger tablet surface area per unit mass of bropirimine and the higher ratio of hydrophilic excipients in a tablet. In the fasted state, the bioavailability of bropirimine after oral administration of tablets tended to reflect the in vitro dissolution characteristics. The bioavailability after administration of tablets with slow in vitro dissolution rate was increased by food intake due to the in vivo dissolution increased in the fed state, while the postprandial effect on the bioavailability of tablets with fast in vitro dissolution rate was not clearly observed. In the fed state, there were no differences in the plasma concentration profile and pharmacokinetic parameters of bropirimine between the tablets with a slow and a fast in vitro dissolution rate. This suggests that the postprandial administration of bropirimine tablets may maximize the bioavailability without distinction of the in vitro dissolution rate.

Influence of Tablet Formulation and Size on the in Vztro Sustained-Release Behavior of Metoprolol Tartrate from Hydrophilic Matrices

Metoprolol tartrate sustained-release tablets were manufactured in 2.8, 7.0 and 10.0 mm diameters. In order to achieve the sustained release of active ingredients, the hydrophilic cellulose polymers methylcellulose, hydroxypropylcellulose and sodium carboxymethylcellulose were used either alone or in combination. It was investigated, in particular, whether the mini-tablets encased in hard gelatine capsules as multiple units allow for the sustained release of the basic active ingredient, which is highly soluble in the acidic pH.While a sustained release is possible from the 7.0 and 10.0 mm diameter tablets formulated on the basis of HPC and NaCMC mixtures, tablets with 2.8 mm diameter do not allow for an adequate control of metoprolol tartrate release during the gastrointestinal passage. Active ingredient release in the range of up to 80 % release and the tablet surface area above a minimum of approximately 300 mm2 are correlated in a linear manner.

The effect of storage at ambient humidity on the BET-specific surface area of tablets compacted from different materials

Tablets compacted from both water soluble and water insoluble particulate solids showed no change in BET-specific surface area when transferred immediately after ejection from the die in a dry atmosphere. Storage at ambient humidity resulted in an irreversible decrease in surface area, caused by capillary condensation of moisture and blocking of pores in the tablet. Nitrogen physisorption isotherms performed on crystalline β-lactose tablets demonstrated diminution of the mesopore surface area.

The effect of moisture sorption on the strenght and internal surface area of lactose tablets

Abstract Tablets compacted from α-lactose monohydrate and from roller dried β-lactose both show time-dependent moiture uptake when exposed to an ambient humid atmosphere. Moisture sorption tends to reach a plateau within 10 min and is accompanied by a decrease in both crushing strength and specific BET-surface area of the tablets. Subsequent storage of the tablets in a dry atmosphere results in an increase in strength but no change in surface area. The tablets show no moisture uptake, nor any change in strength and surface area when transferred immediately after ejection from the die in a dry atmosphere. There changes in crushing strength endorse the need to standardize the time between tabllet ejection and strength measurement. Concerning the BET-specific surface area, it is recommended to suppress blocking of small pores by transferring the tablets immediately after ejection from the die into a dry nitrogen atmosphere for transport to the gas-adsorption apparatus.

カードランの製剤への応用 カードラン錠の調製とｉｎ ｖｉｔｒｏ薬物放出の評価

An application of curdlan, a natural β-1, 3-glucan, to controlled drug delivery was investigated in a form of oral dosage form. Theophylline was chosen as a model drug to be incorporated with curdlan in a tablet. It was found that the drug release rate from the tablets prepared from spray-dried particles of curdlan/theophylline was constant up to 8 hr in vitro studies. Since theophylline release was not influenced by pH or various ions, curdlan tablets could control the drug release in physiological fluids after oral administration. Drug release was estimated to be diffusion controlled by applying the release data to Higuchi's equation. The theophylline release profile from the curdlan tablets was compared with those from 5 kinds of commercially obtained sustained release tablets in pH 1.2 medium for 2 hrs followed by in pH 6.8 medium for 6 hrs at 37°C. In addition to theophylline, release profiles of acetaminophen, propranolol hydrochloride and salbutamol sulfate were also obtained from their curdlan tablets. Although the release rates were influenced by their solubilities, each drug release was sustained greatly compared with corresponding drug powder. Adjustment of drug content in the tablets and of tablet surface area allows formulation of the desired preparation.

Moisture adsorption and tabletting. III. Effect on tablet strenght-post compaction storage time profiles

The effect of air humidity on the post compaction changes in tensile strength of tablets of three test materials, saccharose, sodium chloride and dicalcium hydrogen phosphate dihydrate, was assessed during storage of the tablets for up to 168 h. For saccharose and sodium chloride also the changes in tablet permeametry surface area at storage times up to 24 h was measured. For tablets of saccharose and sodium chloride, the tablet strength increased generally during the storage. An increased air humidity increased both the rate and the degree of the increase in tablet strength, i.e., the storage time after which measurements of tablet data are performed is of importance when the compactibility of a material is evaluated. However, when tablets were stored at or above the critical relative humidity, the tablet strength decreased after a few hours storage. For tablets of dicalcium hydrogen phosphate dihydrate, the tablet strength did not vary with time or storage condition. For tablets of saccharose and sodium chloride, the surface area generally decreased with storage time and the effect was more pronounced with increased storage humidity. Hence, a relationship between the tablet strength and tablet surface area was found. Thus, the changes in tablet strength during storage are probably a result of a rearrangement of solid material within the tablet which is mediated or facilitated by sorbed water.

Consolidation and compaction of powder mixtures. I. Binary mixtures of same particle size fractions of different types of crystalline lactose

Binary powder mixtures of four different types of crystalline lactose: α-lactose monohydrate, anhydrous α-lactose, roller-dried β-lactose and crystalline β-lactose, were compressed into tablets. The results showed a proportional intercorrelation of the crushing strength and internal specific surface area of the tablets, respectively, with the composition of the powder blend, when compressed from binary mixtures of same particle size fraction. All data were found to fit the unique relationship between the crushing strength and the internal specific surface area of crystalline lactose tablets. It is concluded that binary mixtures of same particle size fractions of different types of crystalline lactose exhibit no interaction between the components during consolidation.

Compression characteristics of granulated materials II. Evaluation of granule fragmentation during compression by tablet permeability and porosity measurements

Lactose was granulated with 5% (w/w) polyvinylpyrrolidone as a binder with a wet massing-screening procedure. Fourteen granulations were produced by using different amounts and types of solvent for the binder during the agglomeration procedure. After the granulation, the size fraction 500–710 μm was separated from each granulation for investigation. The granules were characterised on water and binder content, and granule porosity and friability. Both the porosity and friability of the granules were affected by the process conditions. However, there was no correlation between these parameters, which indicates that one surface property of the granule i.e., the ability to withstand attrition, can be different from the overall granule strength. The volume reduction behaviour during compaction was evaluated by measuring tablet permeability and tablet porosity as a function of compaction pressure. The results indicate that the granules became denser at low compaction pressures. It is therefore difficult to use the changes in porosity with compaction pressure as a measure of the degree of granule fragmentation during compression. The tablet permeability as a function of compaction pressure varied among the granulations which indicates that the ability to break down during compression, i.e., the granule fragmentation, varied. It is suggested that changes in tablet permeability with compaction pressure can be used as a measure of this property. The difficulty of defining the intergranular pore space in the tablet will affect the calculation of the tablet surface area. However, the results indicate that in the pressure range used for the permeametry measurements, the total porosity is probably fairly close to the intergranular pore space. Thus, it is suggested that surface area—compaction pressure profiles give a reasonable estimate of the degree of granule fragmentation during compression.

Moisture adsorption and tabletting. II. The effect on tensile strength and air permeability of the relative humidity during storage of tablets of 3 crystalline materials

The effect of moisture adsorption on mechanical strength and air permeability of tablets during storage was studied. Three crystalline substances were used, two water-soluble (saccharose and sodium chloride) each represented by two size fractions and one practically insoluble (calcium hydrogen phosphate). Tablets were stored in a series of RH (33-100%) before measurement of tablet strength and permeability. Tablets were also stored for an additional period of time at a low RH whereafter the tablets were characterized again. For saccharose, an increase in RH during storage resulted in an increase in tensile strength up to a certain level and to a decrease in tablet surface area. This is probably a result of a rearrangement of molecules at the particle surfaces by the action of adsorbed water leading to a formation of solid bridges. A less pronounced effect was obtained for the finer fraction of sodium chloride, whereas no such effect was obtained for the coarser fraction and for calcium hydrogen phosphate. At high RH, the tablet strength decreased in most cases probably because condensed water disturbed intermolecular attraction forces between particles in the tablets. Storage at low RH of transferred tablets did not change the tablet strength or the tablet surface area, i.e. the tablets were at this RH unaffected by adsorbed moisture. Exceptions were transfer of saccharose and sodium chloride tablets from an RH in which the materials had begun to deliquesce. In these cases dissolved material crystallized in the tablet and the formation of solid bridges increased the tablet strength.

The Relationship of Theophylline Release with Tablet Surface Area and Aspect Ratio from a New Matrix Tablet Formulation

The Relationship of Theophylline Release with Tablet Surface Area and Aspect Ratio from a New Matrix Tablet Formulation

Importance of drug type, tablet shape and added diluents on drug release kinetics from hydroxypropylmethylcellulose matrix tablets

The dissolution of 7 drugs from hydroxypropylmethylcellulose (HPMC) matrices have been examined to determine the time exponent ( t n ) required to produce linear dissolution profiles. A value of n = ~ 0.67 was obtained for time-dependent release for soluble drugs, the precise values being 0.71, 0.65, 0.67 and 0.64 for promethazine hydrochloride, aminophylline, propranolol hydrochloride and theophylline, respectively. The insoluble drugs, indomethacin and diazepam, displayed values of n = 0.90 and 0.82 indicating a near zero-order release. Matrices containing tetracycline hydrochloride, however, showed a value of n = 0.45 and displayed complex release patterns and lower release rates than anticipated on the basis of solubility. Replacement of HPMC by calcium phosphate or lactose increased the dissolution rates of promethazine hydrochloride although the values of n were unchanged. Differences in release rates between lactose and calcium phosphate replacement occurred only when matrices contained high levels of the diluents. A straight line relationship existed between release rates and tablet surface area for HPMC tablets containing promethazine hydrochloride.

Studies of tableting properties of lactose. IX. The relationship between particle structure and compactibility of crystalline lactose

In order to study the relation between the compactibility and particle texture of crystalline lactose, a wide variety of samples, differing in particle size, texture, water content and α/β ratio, was investigated. It appeared that the binding capacity of the products was directly related to the powder surface area, determined by gasadsorption measurements. By this technique, it could be established that the values of the tablet surface areas obtained were very unreliable. A plausible explanation for this seems to be the occurrence of capillary condensation in the pores of the tablets. By taking this aspect into account, a relation was obtained between tablet strength and tablet surface area. From this it is concluded that the mechanism of consolidation and the mechanism of binding must be the same for all products.

Studies on tableting properties of lactose. Part III. The consolidation behaviour of sieve fractions of crystalline alpha-lactose monohydrate.

The consolidation and compaction behaviour of sieve fractions of crystalline alpha-lactose monohydrate were studied. From mercury porosimetry measurements tablet pore surface areas were derived. At a certain compaction load it appeared that tablets compressed from small particles were generally stronger and showed a larger surface area than compacts prepared from coarse sieve fractions. By plotting compact strength against pore surface area, a unique linear relationship was obtained. From these results it can be concluded that the actual tablet surface area, being a function of both the initial particle size and applied compaction pressure, is responsible for the compact strength.

Studies on direct compression of tablets XIV. The effect of powder fineness on the relation between tablet permeametry surface area and compaction pressure

Five size fractions in the size range 5 to 180 μm of four materials (sodium chloride, sodium bicarbonate, sodium citrate and lactose) were compressed at pressures up to 200 MPa in an instrumented single-punch press. The permeabilities of the tablets were measured in a transient permeameter and the specific surface areas were calculated according to the permeability equation corrected for slip flow. The surface area of all tabletted materials increased approximately linearly within the whole pressure range. A more marked increase was obtained for the materials consolidating to a large extent by fragmentation (sodium citrate and lactose). For all materials, the finer size fractions gave larger absolute increase in surface area with pressure than the coarser, while for the relative increase in tablet surface area with pressure the reverse applied. A linear relationship was found between the increase in tablet surface area with pressure and the surface area of the starting material to the power of 2 3 . It is suggested that this relation can be used as a means of describing the fragmentation propensity of a material.

Studies on direct compression of tablets X. Measurement of tablet surface area by permeametry

A method for measuring the permeability of tablets was developed. The specific surface areas of the tablets were then deduced using the permeability equation corrected for slip flow. The method was tested on some experimental parameters which had only a minor effect on the tablet surface area. The effect of compaction pressure on tablet surface area, obtained using both a gas adsorption method and a permeametry technique, were then studied for sodium chloride and saccharose (fraction 212–250 μm). The two methods gave similar surface area-pressure curves up to 150 MPa, both substances showing increasing surface area with pressure but a faster increase for saccharose. The permeametry surface area curves continued to increase within the whole pressure range, while the gas adsorption surface area levelled out for saccharose and decreased at the highest pressures for sodium chloride.

Studies on direct compression of tablets. XL Characterization of particle fragmentation during compaction by permeametry measurements of tablets☆

Abstract The usefulness of measuring tablet surface areas by a permeametry technique for the characterization of particle fragmentation during compaction was evaluated. Eight materials (sieve fraction 212–250 μm) with varying and documented consolidation behavior were compacted at a series of pressures in the range 20–200 MPa. The permeability of the tablets was measured and the specific surface area of the tablets was calculated. For all materials the tablet surface area increased with increased compaction pressure within the pressure range studied. However the slope of the curves differed between the materials and they could be rank ordered in agreement with earlier experiences of their fragmentation propensity. The permeametry procedure therefore seems acceptable for estimating particle fragmentation during compaction.

The Measurement of Tablet Surface Area by Permeametry

The Measurement of Tablet Surface Area by Permeametry

Effect of slugging pressure on the properties of granules and tablets prepared from potassium phenethicillin.

The mechanism of preparing compacts by precompression has been investigated. The influence of slugging pressure on the bulk and tapped density, particle size distribution and the surface area of precompressed granules has been examined. The slugged granules have been tableted and the effect of compaction force on the weight uniformity, friability, crushing strength, disintegration time, dissolution rate and internal surface area of the tablets has been studied. The results show that the granules obtained from 15.9 mm slugs manufactured at low compaction forces (e.g. 49 MNm-2) had a lower bulk density, higher friability and larger surface area than those made at higher compaction pressures (e.g. 196 MNm-2). The lighter granules compacted into stronger tablets over a range of compaction forces and the effect was attributed to greater intergranular bonding caused by increased plastic flow.

Drug Release from Wax Matrices II: Application of a Mixture Theory to the Sulfanilamide–Wax System

Using the T. Higuchi relationship for the release of a drug from a solid matrix, a hydrogenated castor oil–propylene glycol monostearate–sulfanilamide system has been investigated. Plots of the amount of drug released per unit of tablet surface area exposed as a function of the square root of time enabled comparison of the release for various concentrations of drug, and the calculation of the apparent tortuosity values. A model based on the Bruggeman mixture relationship for a two-phase system has been used and equations were derived for the prediction of theoretical tortuosity values as a function of porosity due to drug. These theoretical values for tortuosity appear to follow a skewed convex parabolic function. The experimental results obtained compared well with the theoretical predictions.