2006 Ohio Student Research Forum

Abstract

Insulin Particle Formation Using Supercritical Carbon Dioxide
Laura Ensign
Ohio State University
Department of Chemical & Biomolecular Engineering
Mentor(s): Jeff Ellis, Dr. David Tomasko

It has been proven that certain medications, such as insulin, can effectively be administered by a pulmonary route. Particle size and uniformity is very critical for reliable dosage levels. Current mechanical methods for particle formation such as grinding or milling are unsuitable for biological materials. Many innovative particle-engineering methods that utilize the advantages of supercritical fluids as solvents or anti-solvents have been developed to replace mechanical methods. One such process, ASES (Aerosol Solvent Extraction System) has been shown to produce particles of the ideal size to administer by inhalation (1-5 microns) and uniform distribution necessary for reliable dosage. Using supercritical carbon dioxide as the antisolvent has many processing advantages: relatively low “bio-friendly” critical temperature, non-toxic, inexpensive, and requires no extra separation steps. Key variables in the ASES process include drug solution flow rate, antisolvent flow rate, composition of drug solution and antisolvent, temperature, and pressure. Preliminary experiments that explored the effects of these variables on particle morphology were conducted using Bovine Serum Albumin (BSA) as a less-expensive model system. Upon discovering the optimum processing conditions for BSA, these conditions will be used to start work with insulin. The goal of producing insulin particles for inhalation is to be obtained through collaboration with Ventaira Pharmaceuticals. They have developed a technology referred to as “electrohydrodynamic aerosolization” (EHD) that is currently being applied to asthma inhalers. They plan to adapt the technology to developing an inhalable insulin product. Their vast knowledge and experience in modifying the surface of particles to aid inhalation and absorption into the lungs has the potential for improving upon the drawbacks of the currently available product.