Supercritical Process Creates Small, Uniform Powders

Powder processing industries, in particular the pharmaceutical industry, still struggle with such established technologies as crystallization, drying, and milling to produce powders of the right particle size and size distribution. Today's drug makers have these techniques "down to a science," but every product processes differently due to batch-to-batch variation, residual solvent, and statically charged particles. Particle size and quality are especially important for new inhalable and suspension-injectibles (see related story: NanoCrystals Improve Prospects For Insoluble Drugs).

At least ten leading pharmaceutical companies think that supercritical fluid (SCF) formulations may be the answer. That's how many firms have signed collaborative agreements with Bradford Particle Design (Bradford, UK), which specializes in SCF processing of pharmaceutical powders. Bradford was formed in 1995 to develop and commercialize a new chemical powder technique, SEDS (Solution Enhanced Dispersion by Supercritical fluids), discovered at the University of Bradford's Department of Pharmaceutical Technology by Peter York and Mazen Hanna.

SEDS offers a radically new approach that allows direct production of highly specified end-product powders and powder-formulations of chemicals, in particular pharmaceuticals, in a simple one-step process. Bradford is focusing on pharmaceuticals, but the technology can also be applied in other industrial sectors such as agrochemicals, explosives, specialty chemicals, photographic emulsions, and coatings.

SEDS uses a specially designed nozzle to aerosolize a dispersion of pharmaceutical active, solvent, and supercritical CO₂. The dispersion properties of the supercritical fluid break up the solution stream to provide the right particle size, while CO₂'s extractive properties remove the solvent, resulting in dry particles. This single process precipitates the pharmaceutical compound in the form of particles with controlled size, density and crystallinity. The technique may also be used to co-precipitate novel combinations of compounds. Product is recovered by simple filtration, whereas both CO₂ and solvent are recovered and recycled.

"SEDS is ideal for developing new chemical entities, as well as for biopharm products," said Steven Walker, Bradford's Director of Development. For proteins, SEDS is essentially a dewatering process that does not disturb secondary or tertiary protein structure. We've achieved controlled particle sizes, from 500 nm to about 50 microns, in a controlled fashion for either chemical or biopharm drugs.

Walker points out that SEDS is not an off-the-shelf technology and will require a dedicated plant. "Everybody puts on a blank look when you mention supercritical CO₂," he stated, but the technology is so widespread in the food industry it's only a matter of time before it will catch on for drugs as well." The basic equipment for generating supercritical CO₂ is available today, but the nozzle has only been scaled up to handle pilot plant quantities.

"We're designing a production unit right now," Walker said, "but in the meantime we're targeting highly active drug entities where quantities up to a hundred kilos per year or so will make a difference, specifically, inhalables and proteins. These types of products are appropriate for the manufacturing scale we can support in the very short term. Other, more lucrative markets await us when we can offer SEDS on a full production scale."

Bradford recently signed an agreement with PowderJect Pharmaceuticals plc (London) by which SEDS will fuel development of PowderJect's commercialization of its proprietary, needle-free drug delivery system.

Under the terms of the agreement, PowderJect will receive a worldwide license to use BPD's SEDS (Solution Enhanced Dispersion by Supercritical fluids) technologies to develop and commercialize pharmaceutical products in combination with PowderJect's proprietary powder injection systems. In exchange, BPD will receive about $3 million over the next three years in signature fees, research and development funding and milestone payments. In addition, for products utilizing the patented BPD technology, BPD will receive a limited proportion of PowderJect's downstream client revenue.

For more information: Steven Walker, Director of Development, BPD, 49 Listerhills Science Park, Campus Rd., Bradford BD7 1HR, UK. Tel: +44-1274-305-540. Fax: +44-1274-305-570. Email: x11648@bradford.ac.uk.