Gerad Klaas Bolhuis

Effect of water on deformation and bonding of pregelatinized starch compacts

This paper evaluates the tabletting process of pregelatinized starch with different moisture contents on the basis of the stress deformation curve. Simplification of the stress deformation curve enables the amount of elastically stored energy to be calculated. That stored energy, which is the driving force for relaxation of tablets, increases with compaction speed and decreases with increasing water activity of the material. This paper suggests a relation between absorbed water and stored energy. Interparticle bonding, however, also decreases with increasing amounts of adsorbed water. The decrease in stored energy with increasing water activity of the pregelatinized starch tends to produce stronger tablets at higher water activities, whereas the decrease of particle bonding with increasing water activity tends to produce weaker tablets at higher water activities. Given these two counteracting effects, the final tablet strength is a balance between viscoelasticity and bonding, resulting in a water activity where tablet strength has a maximum. In this case, the optimum water activity is about 0.70.

Inulin as filler-binder for tablets prepared by direct compaction

The tabletting properties of a number of different amorphous inulin types were investigated. The types varied with respect to chain length, particle size and amount of included air in the particles. Powder flow properties and densities of the different types were investigated. Just as expected, it was found that the flow properties improved with increased particle size of the material. Compactibility was investigated by compression of tablets on a compaction simulator, simulating the compression on high-speed tabletting machines. The bonding capacity of all inulins was high. However, the lubricant sensitivity strongly varied among the different types of inulin. Generally, amorphous materials such as starches are highly lubricant sensitive, because they show ductile behaviour upon compaction. On the other hand, crystalline materials such as dicalcium phosphate dihydrate have a low lubricant sensitivity, because they fragment during compaction. A high lubricant sensitivity was indeed found for amorphous inulins with a low amount of entrapped air. In contrast, the lubricant sensitivity of the amorphous inulin was low when particles containing large amounts of air were compressed. Obviously entrapped air induces fragmentation of the powder particles by which the lubricant film, covering the particles, was destroyed. Tablets prepared from inulin did not disintegrate but they dissolved when incubated in water. The disintegration/dissolution time increased with decreasing chain length of the inulin. The addition of a disintegrant reduced the disintegration time. The somewhat slower dissolution of the longer chain inulin can be an advantage for chewable tablets or lozenges. It was concluded that inulin with large amounts of entrapped air is a good filler-binder and an attractive alternative to commonly used filler-binders.

DC calcium lactate, a new filler-binder for direct compaction of tablets.

In this paper, a directly compressible form of calcium lactate is introduced as a filler-binder for direct compaction of tablets. Calcium lactate is one of the most important calcium sources and has, in comparison with other organic calcium salts, a good solubility and bioavailability. Two different modifications, calcium lactate trihydrate and calcium lactate pentahydrate are described in the main pharmacopoeias. This paper describes that the compaction properties of calcium lactate pentahydrate (Puracal DC) are much better than those of the calcium lactate trihydrate (Puracal TP). Calcium lactate pentahydrate has better compaction properties than dicalcium phosphate dihydrate, even if lubricated with magnesium stearate. Moreover, as a consequence of its crystalline structure, calcium lactate pentahydrate has a low compaction speed sensitivity. This means that, in combination with its excellent flow properties, calcium lactate pentahydrate is a suitable filler-binder in tablets prepared by high-speed compaction. In a number of formulation examples it will be illustrated that tablets containing calcium lactate pentahydrate as main or additional filler-binder have a short disintegration time and a fast drug release. Directly compressible calcium lactate can be considered as a promising excipient in both pharmaceutical tablets and tablets for the nutraceutical market.

Compaction properties of isomalt

Although other polyols have been described extensively as filler-binders in direct compaction of tablets, the polyol isomalt is rather unknown as pharmaceutical excipient, in spite of its description in all the main pharmacopoeias. In this paper the compaction properties of different types of ispomalt were studied. The types used were the standard product sieved isomalt, milled isomalt and two types of agglomerated isomalt with a different ratio between 6-O-alpha-d-glucopyranosyl-d-sorbitol (GPS) and 1-O-alpha-d-glucopyranosyl-d-mannitol dihydrate (GPM). Powder flow properties, specific surface area and densities of the different types were investigated. Compactibility was investigated by compression of the tablets on a compaction simulator, simulating the compression on high-speed tabletting machines. Lubricant sensitivity was measured by compressing unlubricated tablets and tablets lubricated with 1% magnesium stearate on an instrumented hydraulic press. Sieved isomalt had excellent flow properties but the compactibility was found to be poor whereas the lubricant sensitivity was high. Milling resulted in both a strong increase in compactibility as an effect of the higher surface area for bonding and a decrease in lubricant sensitivity as an effect of the higher surface area to be coated with magnesium stearate. However, the flow properties of milled isomalt were too bad for use as filler-binder in direct compaction. Just as could be expected, agglomeration of milled isomalt by fluid bed agglomeration improved flowability. The good compaction properties and the low lubricant sensitivity were maintained. This effect is caused by an early fragmentation of the agglomerated material during the compaction process, producing clean, lubricant-free particles and a high surface for bonding. The different GPS/GPM ratios of the agglomerated isomalt types studied had no significant effect on the compaction properties.

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.

Hollow filler-binders as excipients for direct compaction

AbstractPurpose. As an effect of their plastic deformation behavior, ductile materials create a large surface for bonding during compaction. However, a serious drawback is their high lubricant sensitivity, preventing the formation of strong bonds. The purpose of this study was both an increase in compactibility and a reduction of the lubricant sensitivity of ductile filler-binders by using hollow particles. This was illustrated for inulin. Methods. Both solid and hollow inulin particles were prepared by spray-drying. Unlubricated tablets and tablets containing 0.5% magnesium stearate were compressed in a compaction simulator, operating at 300 mm/s. The tablet crushing strength was determined with a Schleuniger apparatus. Results. The compaction of unlubricated, solid inulin particles showed that the product had good compatibility. This was caused by plastic deformation of the ductile, amorphous material under load, creating a large surface for bonding. After lubrication, however, the bonding properties decreased significantly, which was caused by the presence of a lubricant film. Hollow inulin particles have an increased compactibility as compared with solid particles and a strongly reduced lubricant sensitivity. Scanning electron micrographs show that hollow particles fragment before they start plastic deformation. This fragmentation behavior is supported by tablet surface area measurements and calculation of the buckling strength. This effect was responsible for both a higher crushing strength and a lower lubricant sensitivity as compared with solid inulin particles. Conclusions. Compactibility of inulin particles can be increased, and lubricant sensitivity can be decreased by using hollow instead of solid particles.

Tableting properties of an improved spray-dried lactose

Abstract Spray-dried lactose is one of the most widely used filler-binders for direct compaction. The compactibility is a function of both primary particle size and the presence of amorphous lactose. Commercially available spray-dried lactose contains 15-20% amorphous lactose and 80-85% a- lactose monohydrate. A better understanding of the relationship between particle structure, physical properties and mechanisms of consolidation and compaction enabled an improved spray-dried lactose to be developed. The agglomerates of the improved product contain smaller primary a-lactose monohydrate particles than those of regular products. The present study shows that the improved spray-dried lactose has better compaction properties than regular spray-dried lactose.