EFFECT OF PROCESS VARIABLES ON THE IN-VITRO DEGRADATION OF PROTEIN MICROSPHERES

Particulate drug delivery systems are utilised in various areas of mod ern medicine. We have previously described a reproducible in vitro met hod for evaluating protein microspheres intended for parenteral admini stration. In this paper we present the results of experiments assessin g the effect of processing variables such as glutaraldehyde used in pr eparation, scaling up of quantities, iodine labelling, drug loading, l yophilisation and storage time after reconstitution. Using the T-1 and T-50 parameters as derived from the measured volume concentration ver sus time profile for the degradation of protein microspheres, we can e valuate statistically differences presented between the data sets. It was found that T-1 and T-50 parameters were affected by the concentrat ion of glutaraldehyde used in the preparation of protein microspheres. Iodine labelling, drug loading and scaling up batch sizes had no effe ct. Changes due to lyophilisation could not be conclusively shown. Aft er reconstitution, protein microspheres exhibit a decreasing resistanc e to proteolytic degradation, this decreased physical stability on sto rage appears to increase with time.