K. Zuurman

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.

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.

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.

The effect of dry granulation on the consolidation and compaction of crystalline lactose

Abstract The consolidation and compaction properties of granule fractions prepared by dry granulation (slugging) of α-lactose monohydrate and roller dried β-lactose, respectively, were studied. The results showed that the compactibility of the granule fractions was determined by the type of lactose used and the granule size. The tablets compacted from the granule fractions show a lower compressibility resulting into almost equal crushing strength but a higher specific BET-surface area as compared to the surface area of the slugs. Influence of granule size on tablet strength points to a relation between outside surface area of granules and tablet strength. Obviously, granule particles sustain their integrity to some extent during compaction. Air permeability and mercury porosimetry showed that in tablets with equal strength different pore systems can exist. Generally, tablets compacted from fine granule size fractions exhibited finer pore sizes and higher strengths compared to the tablets compacted from coarse size fractions. Furthermore, mercury porosimetry revealed that the whole pore system determines tablet strength. This means that granule particles deform during consolidation. The influence of the starting materials on tablet strength can not be explained by permeametry surface area measurements and mercury porosimetry. It is suggested that differences in the internal structure between the granules of the two lactose types are responsible.

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.

EFFECT OF BINDER ON THE RELATIONSHIP BETWEEN BULK-DENSITY AND COMPACTIBILITY OF LACTOSE GRANULATIONS

Abstract The effect of a binder on the relationship between the bulk density and compactibility of lactose granulations was studied by comparing binderless granules with granules containing hydroxypropylcellulose. Granulations were prepared from different grades of a-lactose monohydrate and anhydrous β-lactose, respectively, using two different wet granulation techniques. The results show that the effect of the binder on tablet strength is independent of the type of lactose used, but is significantly influenced by the consolidation and compaction behaviour of the lactose particles. The effectivity of the binder increases with a decrease of the bulk density of the granule powder bed. Tablets with a high crushing strength can be prepared from porous granules, containing a binder.

Pore formation in tablets compressed from binary mixtures as a result of deformation and relaxation of particles

This paper describes the internal structure of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch. The minimum particle diameter of pregelatinised starch inside tablets compressed from mixtures was calculated from the difference between the initial pore size distribution and the pore size distribution after removal of the starch particles by burning. Subsequently, the tablets were carefully crushed. These powders, consisting of almost only sodium chloride particles, were measured by laser diffraction. It was found that the diameter of the sodium chloride particles hardly changed, whereas the minimum diameter of starch particles strongly decreased during the compaction process. As an effect of the difference in yield pressure, the harder sodium chloride particles cause deformation of the softer starch particles, resulting in a change in particle shape. The pore size distribution of tablets compressed from mixtures of sodium chloride and starch is typically that of viscoelastic materials; the larger pores (>5 microm) change, while the small pores stay constant in number and size. The median pore diameter in tablets compressed from the mixtures is higher than the median pore diameter in tablets compressed from the pure materials. This paper shows that the formation of large pores was the result of the extra porosity expansion of tablets compressed from binary mixtures of sodium chloride and pregelatinised starch.

Effect of Compaction Temperature on Consolidation of Amorphous Copolymers with Different Glass Transition Temperatures

AbstractPurpose. The purpose of this study was to relate the combination of glass transition temperature (Tg) and temperature of measurement with the mechanical and compaction properties of some test materials. Methods. Copolymers with different Tgs were synthesised by free radical copolymerisation of methyl methacrylate with lauryl methacrylate. Elastic moduli were measured by dynamic mechanical analysis at different strain rates and temperatures. Compaction experiments were performed at different compaction speeds and temperatures. Results. The difference between temperature of measurement and Tg appears to determine both elastic modulus and yield strength completely. They both decrease with decreasing difference between temperature of measurement and Tg and increase with strain rate. At temperatures of measurement higher than the Tg, the elastic modulus is extremely low because the materials behave as rubbers. Consequently, the amount of energy stored during compaction decreases when the compaction temperature approaches the Tg and increases with strain rate. When the compaction temperature is higher than the Tg, the amount of stored energy is extremely large. The compaction experiments show that the final tablet porosity is completely determined by stress relaxation phenomena. Consequently, the final tablet porosity follows exactly the same relation as that of stored energy. Conclusions. The final tablet porosity is unequivocally determined by the amount of stored energy. This implies that tablet production at a temperature of about 20 K under the glass transition temperature of the material yields tablets with minimum porosity.

The influence of particles of a minor component on the matrix strength of sodium chloride.

This paper deals with the matrix strength of sodium chloride particles in pure sodium chloride tablets and in tablets compressed from binary mixtures of sodium chloride with low concentrations of pregelatinised starch. Because this study concerns the strength of the sodium chloride matrix, the tablet strength is reflected as a function of the sodium chloride volume fraction in the tablet. Starch particles in the mixture tablets decrease the sodium chloride volume fraction-tensile strength relationship compared with that of pure sodium chloride tablets. To determine the contribution of the sodium chloride matrix to the tablet strength, the starch particles were removed from the mixture tablets by heat treatment. Determination of the strengths of these heat-treated tablets reveals that the sodium chloride matrix strength determines the tablet strength of mixture tablets containing a single matrix of sodium chloride particles. The decrease of the sodium chloride matrix density in the three different tablets (pure sodium chloride tablets, mixture tablets and heat-treated tablets) is reflected by an increase of the median pore size. The matrix in sodium chloride tablets shows a higher tensile strength to median pore size relation than the matrices in the mixture and heat-treated tablets. Based on calculations according to the theory of elastic-brittle fracture, it is suggested that the initial presence of starch particles during tablet compaction causes the pores in the matrices of the mixtures and heat-treated tablets to be relatively more flat and longer. These pores weaken the sodium chloride matrix in the mixture and heat-treated tablets to a larger extent than the shorter, more spherical pores formed during compaction of pure sodium chloride.