G.K. Bolhuis

BONDING CHARACTERISTICS BY SCANNING ELECTRON-MICROSCOPY OF POWDERS MIXED WITH MAGNESIUM STEARATE

Abstract The effect of degree of mixing on the bonding properties of blends of magnesium stearate and tablet excipients is shown to be dependent upon the compression behaviour and bonding mechanism of the excipient studied. Magnesium stearate exercises a maximum effect on excipients such as the starch derivative Amylose V, which undergoes complete plastic deformation without any fragmentation and is bonded by cohesion. The effect on excipients bonded by cold-bonding mechanisms after plastic flow of the crystals, as demonstrated for sodium chloride, is dependent on the extent to which clean, lubricant-free surfaces are formed during compression. The bonding properties of excipients such as dicalcium phosphate dihydrate, which undergo complete fragmentation under pressure, are practically uninfluenced by mixing with magnesium stearate.

Effect of magnesium stearate on bonding and porosity expansion of tablets produced from materials with different consolidation properties

The negative effect of magnesium stearate on tablet strength is widely known. This strength reduction is always considered to be the result of reduction of interparticle bonding. It is also known that interparticle bonding affects relaxation of tablets. Relaxation increases with decreasing bonding. Microcrystalline cellulose is an example of a material with a high lubricant sensitivity, which effect is caused by its plastic deformation behavior during compression. This paper shows for microcrystalline cellulose that the porosity under pressure was equal for unlubricated tablets and for tablets containing 0.5% magnesium stearate. This points to equal densification properties. The lubricated tablets show, however, a much larger relaxation than the tablets without magnesium stearate. This difference can be ascribed to the reduction of interparticle bonding by the lubricant, because a strong interparticle bonding counteracts tablet relaxation. In contrast to microcrystalline cellulose, aggregated gamma-sorbitol (Karion Instant) has a low lubricant sensitivity. Both porosity under pressure and tablet relaxation were found to be equal for lubricated and unlubricated sorbitol tablets. This phenomenon is caused by the particle structure of gamma-sorbitol. During compression, a lubricant film will be destroyed by fragmentation of the sorbitol aggregates. For this reason, magnesium stearate will hardly affect the interparticle bonding between sorbitol particles and hence have only a small or no effect on tablet relaxation.

Porosity expansion of tablets as a result of bonding and deformation of particulate solids

Abstract This paper describes the tabletting process of y-sorbitol on the basis of the stress-deformation curve. This curve distinguishes between small, elastic deformation and large, viscous deformation. Small deformations can be quantified by the dynamic Youngs modulus. The results demonstrated an effect of both rate of strain and initial particle size on the Youngs modulus. The yield strength of compacts is a quantification of large deformations. There appeared to be an effect of strain rate on yield strength, but no clear relation between initial particle size and yield strength. The study relates elastic deformation with storage of elastic energy. The amount of stored energy was found to increase with compaction speed, and is postulated to be the driving force for changes of tablet porosities after compression. The attraction between particles causes resistance against porosity expansion, and is defined as expansion capacity. The expansion capacity showed no relation to compaction speed. It is therefore concluded that the effect of compaction speed on tablet properties is purely an effect of the amount of stored energy. The reciprocal value of expansion capacity demonstrated a direct relation with the constant that fits the relation between tablet strength and porosity. The expansion capacity is hence a quantification of bonding.

STUDIES ON TABLETING PROPERTIES OF LACTOSE .3. THE CONSOLIDATION BEHAVIOR OF SIEVE FRACTIONS OF CRYSTALLINE ALPHA-LACTOSE MONOHYDRATE

The consolidation and compaction behaviour of sieve fractions of crystalline α-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.

THE RELATIONSHIP BETWEEN BULK-DENSITY AND COMPACTIBILITY OF LACTOSE GRANULATIONS

The relationship between the bulk density and the compactibility of lactose granulations was studied. The granulations were prepared from different α-lactose monohydrate and roller dried β-lactose powders by wet granulation, using different techniques with only water as a binder, or by slugging. The results demonstrate that by the process of granulation of one lactose powder, granules with different bulk densities and different compactibilities can be prepared. In addition to the type of lactose used, the compactibility of the granule fractions is dependent on the bulk density of the granule fraction. Generally, with an increase of the bulk density, the compactibility of a granule fraction decreases. Little variation is observed between the intergranular porosities of the granule fractions. More differences are found between the intragranular porosities of the granule fractions. However, the compactibility of granule fractions of one lactose type is mainly determined by the total porosity of the granule powder bed. Mercury porosimetry determinations on tablets compacted from the granule fractions show a relationship between the tablet pore system and the compact strength: compression of granulations with a low bulk density results into tablets with a small average pore diameter and a high crushing strength. Obviously, the possibility to deform a granule fraction during compression, the deformation potential, is determined by the total porosity of the powder bed. A high deformation potential, i.e., a high compactibility, can be obtained by using a granulation procedure in which granulations with a low bulk density are produced.

Studies on tableting properties of lactose. Part 2. Consolidation and compaction of different types of crystalline lactose

Lactose is available in several crystalline forms, which differ in binding properties. A new method of estimating the fragmentation propensity was applied to investigate the consolidation and compaction behaviour of this excipient for direct compression. Mercury porosimetry was used to demonstrate that crystalline lactose fragments during compaction. Tablet strength was found to be dependent on the degree of fragmentation only. This finding indicates that the nature of the actual binding must be the same for the different types of crystalline lactose.

Tensile strength of tablets containing two materials with a different compaction behaviour

The tensile strength of tablets compressed from binary mixtures is in general not linearly related to the strength of tablets prepared from single materials; in many cases it shows a decreased tensile strength relative to interpolation. The materials used in this study, sodium chloride and pregelatinised starch, are both plastically deforming materials, but have a different densification and relaxation behaviour. The yield pressure of the binary mixtures shows an almost linear relationship. As an effect of their lower yield pressure, starch particles yield earlier than sodium chloride particles. The following enclosure prevents some sodium chloride particles to yield or crack. The relaxation of the tablets is higher than the relaxation calculated by linear interpolation of the relaxation behaviour of the two pure materials. The difference between the measured porosity expansion and the data obtained by linear interpolation can be considered as a measure for the reduced interparticle bonding. SEM-photographs indicate that the reduced interparticle bonding is caused by the low adhesive forces. The measured decrease of the tensile strength of the tablets is also considered to be the result of reduced interparticle bonding. In this paper it is shown that there exists a similar relationship between the tensile strength reduction and the percentage of starch on the one hand and the extra porosity expansion and the starch percentage on the other hand.

Stress relaxation of compacts produced from viscoelastic materials

Stress relaxation of tablets is a phenomenon that is known to be related to elastic deformation of particles. Expressions of stress relaxation are tablet expansion and capping. It has been shown that there is a direct relation between the changes in volume of the tablet and the amount of stored energy, calculated from the elastic modulus and the yield strength of the material. The relations are, however, different for the different materials. On the basis of the assumption that the increase in tablet volume is an expression of stress relaxation and stored energy is the driving force for it, there should be a counteracting force that prevents a compact from expansion. This paper shows that the counteracting force is determined by particle bonding, quantified by the Ryshkewitch-Duckworth relation and friction of the tablet with the die wall, quantified by the ejection pressure. The data presented here suggest that the final tablet porosity is unequivocally determined by stored energy, particle attraction and friction of the tablet with the die wall. All tablets that were capped showed both high stored energies and large particle bonding. From this observation it is concluded that porous and capped tablets suffer from the same problem, but the expression stress relaxation is different for the different materials.

Improvement of dissolution of poorly soluble drugs by solid deposition on a super disintegrant .2. The choice of super disintegrants and effect of granulation

It is demonstrated that the dissolution from capsules and tablets of poorly soluble, hydrophobic drugs can be strongly improved by solid deposition of the drug upon hydrophilic, strongly swelling carriers like the super disintegrants sodium starch glycolate and croscarmellose sodium. As an effect of its lower swelling power, the super disintegrant crospovidone is far less effective than the other super disintegrants. Wet granulation of poorly soluble drugs with high concentrations of sodium starch glycolate resulted likewise in a strongly improved drug release and bioavailability from capsules and tablets. It was found, however, that granules containing a too high concentration of the super disintegrant slow down the drug release from tablets. This effect is caused by the formation of a viscous barrier of the super disintegrant in the granules during the dissolution process.

EVALUATION OF ANHYDROUS ALPHA-LACTOSE, A NEW EXCIPIENT IN DIRECT COMPRESSION

AbstractDifferent forms of lactose are available for direct compression of tablets. The use of spray-dried lactose, which has good flow and compressibility characteristics, is limited by its stability when stored under humid conditions. Sieved crystalline fractions of α-lactose monohydrate such as the 100 mesh fraction, have very good flow properties and an outstanding stability, but the compressibility is so poor, that it can be used only in combination with other filler-binders, like microcrystalline cellulose. A third form of lactose, increasingly used in direct compression is anhydrous lactose. The commercially available products generally consist of an excess of β next to α-lactose. They both have good binding and stability characteristics, but a flowability which is less than optimum. The latter is caused by the rather irregular particle shape and the relatively high amount of fines. A newly developed form of lactose is anhydrous α-lactose. It is prepared by dehydration of α-lactose monohydrate. Bin...