Investigation of Supercritical Fluid Technology to Produce Dry Particulate Formulations of Antibody Fragments

Abstract

Investigation of Supercritical Fluid Technology to Produce Dry Particulate Formulations of Antibody Fragments Micro, submicrometre and ultrafine particles are increasingly in demand as they have a broad application in pharmaceutical delivery and needle-free powder injection. Conventional methods of powder preparation including freeze-drying and spray drying have considerable disadvantages for these applications.The use of supercritical fluids for materials' processing is one of the efficient and novel approaches used to achieve high purity micron-sized particles in a single step. The technique of Solution Enhanced Dispersion by Supercritical Fluids (SEDS) dramatically reduces or eliminates the problems associated with current, conventional particle-formation and size-reduction processes. SEDS involves the rapid dispersion, mixing and extraction of a protein solution, anti-solvent and supercritical carbon dioxide. SEDS has been used to produce dry particulate formulations of three antibody fragments (D1.3Fv, 4D5Fab, PEG-4D5Fab) and a whole antibody (CDP850). The aim of this research was to assess affects of the SEDS process on the functionality antibody fragments and antibody.The results demonstrated that dried formulations of antibody fragments and antibody can be produced using the SEDS process. The level of damage caused during SEDS was found to be dependent on choice solvent and protein. The main cause of activity loss was identified as the presence of both water and solvent during SEDS processing. 3 Dedication 4 Table of Contents 5List of Figures 9 List of Tabies 10Chapter One -Introduction proteins the limitations are obvious. Spray drying can induce dénaturation and a low product yield. Milling, which can result in activated surface particles and produce a broad size distribution and fluid energy grinding, which frequently results in electrostatically charged powders, are more efficient for hard and brittle materials than for soft substances like proteins (Moshashaée et al., 2000, Palakodaty et al., 2000.One method of size reduction and particle formation capable of yielding very small particles and a narrow size distribution and devoid of certain drawbacks of conventional techniques, is one that utilises supercritical carbon dioxide. Supercritical fluid technology, and especially the solution enhanced dispersion by supercritical fluids (SEDS) process, has shown great promise in applications such as preparing particulate pharmaceuticals with defined physiochemical properties (Palakodaty etal., 2000).