Jacob Bergsma

A new generation of starch products as excipient in pharmaceutical tablets. I. Preparation and binding properties of high surface area potato starch products

A new pharmaceutical excipient with a high binding capacity was prepared from potato starch by enzymatic degradation, followed by suitable dehydration of the precipitated and filtered retrograded starch to produce high specific surface area products. Thermal dehydration methods like drying at room or elevated temperature and spray-drying resulted in particulate solids with low specific surface area, as measured by nitrogen adsorption, and low compactibility. Both freeze-drying and chemical desiccation, like washing with ethanol or acetone, produced powders with strongly increased specific surface area and increased binding capacity. The compactibility of the final products showed a positive correlation with the specific surface area, changing at high surface areas into constant compactibility. Moreover, the binding capacity appeared to increase with the moisture content of the products.

A new generation of starch products as excipient in pharmaceutical tablets. II. High surface area retrograded pregelatinized potato starch products in sustained-release tablets

Abstract A new linear short-chain starch product was prepared by gelatinization of potato starch followed by enzymatic degradation, precipitation (retrogradation) and filtration. A high specific surface area was subsequently created by washing with ethanol or acetone or freeze-drying. Tablets compressed from a mixture containing the starch product and 30% theophylline at a force of at least 15 kN showed no disintegration and an almost constant (zero-order) sustained drug release. The delivery from these non-porous tablets proved to be a swelling-controlled solvent-activated mechanism, as was confirmed by the slow penetration of a solvent front into the tablet. Drug release proved to be not affected by the incorporation of magnesium stearate into the tablet or the presence of α-amylase in the dissolution medium, both features in contrast to similar tablets compressed from conventional pregelatinized starches, which were prepared by gelatinization followed directly by thermic dehydration. A specific surface area of 1.5 m2/g proved to be a prerequisite for the starch product to control drug release. A high surface area (linear long-chain) amylose product showed a sustained but less linear release profile. Branched short and long-chain products with a high surface area produced disintegrating tablets and are therefore not able to control drug release.

A new generation starch product as excipient in pharmaceutical tablets. III. Parameters affecting controlled drug release from tablets based on high surface area retrograded pregelatinized potato starch

This paper describes the general applicability of a new pregelatinized starch product in directly compressible controlled-release matrix systems. It was prepared by enzymatic degradation of potato starch followed by precipitation (retrogradation), filtration and washing with ethanol. The advantages of the material include ease of tablet preparation, the potential of a constant release rate (zero-order) for an extended period of time and the possibility to incorporate high percentages of drugs with different physicochemical properties. Constant release profiles are the result of solvent penetration into the tablet. For theophylline as test drug, constant release profiles could be realized up to a drug content of 75%. This illustrates the possibility to control the release of highly dosed drugs. Release rates from retrograded pregelatinized starch tablets can be enhanced or decreased to the desired profile by different parameters, like geometries of the tablet, compaction force and the incorporation of additional excipients. For procaine HCl it is demonstrated that larger tablets show slower release rates. The incorporation of soluble excipients like lactose and mannitol results for paracetamol in enhanced release rates. The delivery of bases and their salts can be modified by the incorporation of organic acid or alkaline excipients, as is demonstrated for lidocaine and procaine HCl.