Kemgas, Ecole Polytechnique Team On Pharm Powders

Powder consistency is almost synonymous with pharmaceutical product quality; a fact not lost on Kemgas Ltd. and academic collaborator Ecole Polytechnique of Lausanne (EPL; Lausanne, Switzerland). The two organizations plan to apply novel powder-processing techniques, developed for the chemical industry, to making pharmaceutical-grade powders. Development efforts will focus on improving batch-to-batch powder consistency, a problem that plagues makers of a variety of dosage forms.

Kemgas and EPL have jointly developed and demonstrated, on a laboratory scale, a device known as a segmented flow tubular reactor, which blends fluids and semisolid ingredients in such a way that the powders being manufactured are consistently uniform.

The segmented flow tubular reactor has potential applications in virtually any industry in which powders are a basic component of the finished product. Besides pharmaceuticals, the collaborators are eyeing the paint, plastics, paper, ceramics and electronics industries, some of which have even higher powder quality concerns than pharm.

In conventional powder manufacturing, large batches of ingredients are combined in a tube-shaped reactor or vessel. Under these conditions constituents mix unevenly because particles of different sizes, densities, and surface electrostatics travel through the tube at varying speed: Some clump together on the sides while others, in the center, flow through unimpeded. In the segmented flow tubular reactor, a virtually continuous flow is produced by flowing a large number of micro batches through the reactor, each one separated from its neighbors by a fluid which does not mix with the process liquid. Problems of variations within a batch are eliminated and product uniformity is ensured.

The reactor system consists of three components: mixer, segmenter and the tubular reactor itself. Sometimes reactants are mixed without precipitation before introduction into the reactor. This is the case of precipitation from a homogenous solution, where the precipitating reactant may be generated by thermal hydrolysis of an organic precursor. Nucleation and growth take place in the tubular reactor, whose length defines the reaction time. In this case, the reaction mixture is injected directly into the segmenter, and the mixer is not used.

In some reactions, particles are formed along two parallel growth processes—crystal growth and crystallite aggregation. Both crystallites and aggregates vary in size depending on the physical reaction conditions. In the case of copper oxalate, for example, larger aggregates are formed in the segmented flow tubular reactor and larger crystallites are formed in most batch reactions. This phenomenon is caused by inconsistencies in the batch process, as nucleation and aggregation kinetics are allowed to vary. Varying kinetics definitely influence particle characteristics. For this reason, the precipitate from the continuous tubular reactor exhibits a more regular morphology, even though the product of the batch and continuous process appears to be identical using laser particle size analysis.

The role of flow segmentation in the tubular reactor is demonstrated most easily with homogeneous precipitation reactions. Without segmentation, a laminar velocity gradient develops in a tubular reactor, just as with any fluid in a tube. Particles moving with various speeds according to their axial position in the tube will experience different residence times, leading to wider size distribution. The segmentation feature of the reactor ensures the same residence time for each individual microvolume of reactant.

Kemgas, which specializes in innovative technology for acetylene production, expects to be awarded a patent soon by the European Patent Office for the segmented flow tubular reactor, with a U.S. patent to follow in 1999. The new technology will be marketed through Kemgas.

The segmented flow tubular reactor grew out of work by Kemgas and the EPL on processes for manufacturing marketable calcium salts from carbide lime, a by-product of acetylene production. High-grade calcium salts such as precipitated calcium carbonate is used as filler and extender in a wide range of products, from adhesives and foodstuffs. The PCC market is about four million tons a year and growing at 10% per year.

For more information: Kenneth G. Jackson, president, Kemgas Ltd., B.P. 31, 13 chemin du Levant, 01211, Ferney Voltaire, France. Tel: +33-450-428-095. Fax: +33-450-405-961.