Effect of process variables on the in vitro degradation of protein microspheres

Abstract

Particulate drug delivery systems are utilised in various areas of modern medicine. We have previously described a reproducible in vitro method for evaluating protein microspheres intended for parenteral administration. In this paper we present the results of experiments assessing the effect of processing variables such as glutaraldehyde used in preparation, scaling up of quantities, iodine labelling, drug loading, lyophilisation and storage time after reconstitution. Using the T 1 and T 50 parameters as derived from the measured volume concentration versus time profile for the degradation of protein microspheres, we can evaluate statistically differences presented between the data sets. It was found that T 1 and T 50 parameters were affected by the concentration of glutaraldehyde used in the preparation of protein microspheres. Iodine labelling, drug loading and scaling up batch sizes had no effect. Changes due to lyophilisation could not be conclusively shown. After reconstitution, protein microspheres exhibit a decreasing resistance to proteolytic degradation, this decreased physical stability on storage appears to increase with time.