The patent (No 6,743,447) describes a process to achieve something that has hitherto been thought impossible: producing mannitol in a format that combines the desirable characteristics of a fine particle size, high density, good flowability and solubility in water.
Mannitol is a polyol, a group of compounds that are commonly used as pulverulents in the drug industry. At present, the most commonly used polyol is sorbitol, which has the advantage of being cheap and with a good range of particle size - the aim is generally to match the size of the carrier to the API - which improves processing.
However, the downside of sorbitol is that it is very attractive to water, which gives it a tendency to clump and impairs its flowability, as well as making it unsuitable for use with APIs that are sensitive to water. Meanwhile, xylitol has been used but is expensive and tends to clump.
Mannitol has been put forward as an alternative for some time, but producing a version with the desired characteristics has proved difficult - at least on an industrial scale - and has tended to produce particle sizes that are not optimal in terms of flowability.
The problem is related to its crystalline structure, which favours the creation of large particles that break down into very fine particles, and its low solubility in water.
Roquette has overcome these problems by approaching the problem from reverse. While most researchers have tried to produce fine-sized particles at the outset, the French company's solution has been to start with crystalline mannitol and modify its physical properties through continuous mixing and granulation steps.
Specific details can be obtained by viewing the patent application here.
New pharma superdisintegrant
Meanwhile, Roquette has produced a pharmaceutical-grade version of its sodium starch glycolate, Glycolys, used as a superdisintegrant. There are three products in the pharmaceutical range, including standard, acid-stable and low-viscosity versions.
Pharmaceutical-grade Glycolys is manufactured at Roquette's plant in Lestrem. A Drug Master File for the excipient - clearing its way for use in pharmaceuticals - was registered at the US Food and Drug Administration (FDA) in November 2003.