In vivo evaluation of targeted delivery of biological agents using barium sulfate

This study was aimed to monitor the transit through the intestine by X-ray imaging using barium sulfate (BS) as tracer. The in vitro features of monolithic tablets were correlated with their in vivo behavior in order to provide a tool for the development of targeted formulations containing macromolecular bioactive agents. The impact of BS on various matrices (neutral, ionic) was studied in simulated fluids using the disintegration time (DT) as main parameter. Dry tablets were characterized by spectroscopic methods (X-ray diffraction and Infra-Red) and scanning electron microscopy (SEM). The selected formulations were followed in a beagle dog model. The in vivo and in vitro DT of tablets formulated with BS were compared. Results: anionic excipients carboxymethylcellulose (CMC) and carboxymethylstarch (CMS) protected the active ingredient from the gastric acidity, ensuring its targeted delivery in the intestine. The SEM analysis, before and after transit in simulated fluids, showed that BS remained in the tablets allowing their good follow-up in vivo. The incorporation of 30% protein in tablets with 40% BS had no impact on their behavior. In conclusion, BS and X-ray imagery could be a good alternative to scintigraphy for development of targeted formulations containing high molecular weight bioactive agents.