Biomedical subjects
Publications and source records attributed to Gerad K Bolhuis.
In 1996, Bolhuis and Chowhan compiled a review of excipients that were used for the direct compaction of tablets. This article updates that review because since that time there has been considerable activity in this area. New single component and coprocessed filler-binders have been introduced. In addition, there have been advances in the understanding of how such substances act and hence how they can be optimally designed.
PURPOSE: 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.
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.