European Journal of Pharmaceutics and Biopharmaceutics 2004-03-01

Usage of radiopharmaceuticals in the development of pharmaceutical drug delivery systems: validation of [99mTc]DTPA and [99mTc]ECD.

Mariella Terán, Eduardo Savio, Andrea Paolino, Malcolm Frier

Index: Eur. J. Pharm. Biopharm. 57(2) , 347-52, (2004)

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Abstract

Tablets containing drugs of different lipophilicity, ranitidine and cinarizine, and placebo were prepared and their in vitro behaviour was studied by dissolution and disintegration tests. [(99m)Tc]Diethylenetriamine-pentaacetic acid ([(99m)Tc]DTPA) and [(99m)Tc]ethyl cysteinate dimer ([(99m)Tc]ECD) were used as tracers of the process. Both of them were added to tablets during wet granulation. Dissolution and disintegration profiles were assessed at different pH values (1, 4 and 7). Radioactivity was evaluated in filtered samples and scintigraphic studies were carried out in gamma camera. Stability in dissolution media was confirmed for both tracers under these conditions. Dissolution and disintegration velocity constants were calculated. [(99m)Tc]DTPA proved to be an appropriate tracer for polar drugs such as ranitidine. Nevertheless, it was not a suitable tracer for lipophilic active drugs such as cinarizine. On the other hand, the most lipophilic tracer, [(99m)Tc]ECD, exhibited the opposite behaviour. Scintigraphic studies of the disintegration process did not show significant differences between placebos and tablets containing active drugs. As disintegration is a physical process it does not discriminate between chemical differences in tablet formulations. Both methods complement each other because the dissolution process can be followed when a suitable radiotracer is chosen according to the physicochemical characteristics of the active drug.