Protein Particle Formation for Pulmonary Delivery
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Chemical and Biomolecular Engineering Honors Theses; 2007
Recently, there has been an increased focus on inhalation therapies in drug delivery research. It has been proven that many medications and vaccines can be inhaled in particle form, which has certain advantages. Respiratory diseases such as asthma and emphysema can be more directly treated by administering medications to the lungs. Even for non-respiratory conditions, the large internal surface area of the lungs provides a very effective means for entering the bloodstream. Particle processing of pharmaceuticals is commonly done in batches with toxic organic solvents; a large portion of drug processing costs come from multiple solvent separation steps. Another problem with batch processes is that it is difficult to achieve consistent particle size and distribution. To overcome these issues, many innovative particle engineering methods have been developed using supercritical fluids as the solvents or anti-solvents. One such process, ASES (Aerosol Solvent Extraction System), has proven to yield particles of the ideal size to administer by inhalation (1-5 microns) and uniform distribution necessary for reliable dosage. Also, a supercritical fluid such as CO2, which is gaseous at room temperature, completely separates upon returning to ambient conditions. This process has great potential to increase yield, increase throughput, and decrease processing costs. This purpose of this study is to find trends for development of mathematical models and to show potential for realistically scaling up for industrial production. Key processing variables include drug solution flow rate, antisolvent flow rate, temperature, and pressure. Preliminary experiments explored the effects of these variables on particle morphology using Bovine Serum Albumin (BSA) as a less-expensive model system. It was found that increasing the system pressure decreases the size of the primary particles, but increases agglomeration due to frequency of particle collisions. Increasing the system temperature also decreases the particle size, which indicates the need for a balance between achieving high density and high viscosity in the antisolvent. For this system, solution and antisolvent flow rates appear to have the most pronounced effect on the resulting particles. This would indicate that turbulence and other mass transfer effects are the most important. Furthering studies with BSA on a larger scale will help to understand the effects of scale on the important processing variables. Advisor: Dr. David Tomasko
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