A novel supercritical fluid coating method

A supercritical fluid (SCF) is a fluid above its critical temperature and pressure. SCFs possess low viscosity and high diffusivity, and their density and solvent power are readily tunable by changing the temperature or pressure. The most commonly used SCF is carbon dioxide (scCO2), because of its low critical conditions and high availability. The use of this fluid is also carbon neutral as the CO2 is captured from other industrial processes and can be recycled in use. The interesting properties of SCFs have led to their exploitation in many different fields such as extraction and chromatography. Of relevance to this project is their use in particle engineering. Several techniques have been developed in which nano- and microparticles are produced using SCFs (particularly scCO2). These methods can be more attractive than many conventional particle production techniques because:1. Micro and nano particles with a narrow size distribution can be produced in one step,2. The use of organic solvents can be eliminated or greatly reduced,3. The processes can be less damaging to labile substances, 4. The processes may produce polymorphs that are not obtainable by other means.However, it is difficult to capture these small particles and preserve their properties during subsequent processing. This work therefore focuses on developing methods for collecting such particles directly from SCF precipitation processes and incorporating them into a readily processable form. The focus will be on the processing of materials for the pharmaceutical industry, where the demand for micro and nano particles is high. Specifically, small, precipitated drug particles will be collected/coated onto the surfaces of pharmaceutical excipients (the non-active components of pharmaceuticals) to form products that can be readily converted into dosage forms such as tablets. To achieve this, SCF precipitation methods will be combined with fluidised bed technology.Fluidised beds are used in many industries as reactors, mixers, dryers, agglomerators and coaters. Fluidisation occurs when an upward flow of fluid, usually a gas, through a bed of particles becomes sufficient to support them against gravity. The pressure drop across the bed then equals the bed weight and the particles are free to move. Fluidised beds possess some of the properties of single-phase fluids; of relevance to this project is the fact that they circulate and mix easily. Three strategies for combining fluidisation with SCF particle production are to be investigated: 1) Drugs that are soluble in scCO2 will be dissolved in this fluid under pressure. The resulting solution will then be expanded into a fluidised bed of excipient, maintained at a lower pressure. As the scCO2 expands, it loses its solvent power and the drug will precipitate out onto the excipient particles. 2) Drugs that are not soluble in scCO2 will be dissolved in a solvent such as ethanol. This solution will then be pumped into a bed of excipient fluidised with scCO2. The SCF acts as an antisolvent, causing the drug to precipitate out of solution and onto the surface of the excipient particles.3) Thermally stable drugs will be melted to form a liquid into which scCO2 can be dissolved. The mixture will then be passed into the fluidised bed where the scCO2 will expand, atomising and cooling the liquid drug. Solid drug particles will form that can coat the excipient. The work will include the characterisation of the products from the fluidised beds and their conversion into tablets or other dosage forms. This work will remove one of the major blocks in the acceptance of SCF particle production in industry - the difficulty of integrating the particle formation step into conventional downstream processes. Other users of this technology, outside the pharmaceutical sector, might include companies engaged in the manufacture of food, toners, coatings, chemicals and catalysts.