Pharmaceutical production of nano particles using supercritical or dense gas technology

Full text: The primary aim of our proposed research is to develop pharmaceutical formulations with enhanced pharmacokinetics and increased bioavailability. The particular drug delivery systems of interest are, oral, aerosols, injectable and topical with well-recognised and distinct problems of bioavailability. More than 40% of all drugs in the USP or BP are insoluble or have some problem with solubility. It is estimated in 2000, the total combined sales of drugs that are insoluble or poorly soluble was US$37 billion. Precise and predictable drug delivery is made more possible by producing uniform micron size particles or powders, which can improve the efficiency and effectiveness of therapeutical formulations. Hence the purpose of micronisation is to increase bioavailability and also to allow other modes of administration, eg insulin is a protein, which is an injectable for the treatment of diabetes, but recently particles of 1-4 microns of insulin are in phase 3 clinical trials to deliver the drug to diabetics as an inhalant. In addition aerosolised drugs such as mucolytics, antibiotics, antiinflammatory drugs and hormones have recently been trailed. Finely powdered pharmaceuticals are however difficult to process by current techniques. In spray drying the operating temperatures are often too high for heat sensitive drugs. Thermal degradation of compounds can also be experienced in milling due to high rates of shear and requires high energy inputs and do not produce particles within a narrow range distribution. A relatively new technique which has been used and developed by Eiffel Technologies to produce uniform micron and sub micron size particles is a dense gas process in which the gas is used as an antisolvent to precipitate compounds from solution. Pharmaceutical processing with dense gas is relatively new and is an efficient process for producing high purity micronised particles with defined morphological structures and with a narrow size distribution rate. Dense gas technology using fluids, near or above the critical point, as a solvent or antisolvent have been developed in recent years. Eiffel has considered various dense gas methods as in the production of nano particles. The first method is known as Rapid Expansion of Supercritical Solutions (RESS), and involves expanding a supercritical solution of the drug through a nozzle. Whilst providing very effective methods of producing fine particles, the application of the RESS method is limited by the low solubility of drugs in dense carbon dioxide (which is usually the gas of choice since it is operated at moderate critical temperature of 31.1 degrees centigrade). The second method, known as Gas Antisolvent Process (GAS), involves rapid precipitation of the drug from organic solutions, typically using carbon dioxide as the antisolvent. The third mode which is called the Aerosol Solvent Extraction System (ASES), involves continuous introduction of a solution containing the drug of interest through a nozzle into a flowing dense gas stream