In Vivo

PURPOSE: The suitability of 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 99mTc-sulphur colloid (99mTc-SC) as tracers in gamma Scintigraphy for the evaluation of colon-specific drug delivery systems was assessed in healthy volunteers. METHOD: Sodium chloride core tablets containing either 99mTc-DTPA or 99mTcSC were prepared and compression coated with two different quantities of guar gum. The compression-coated tablets were subjected to gamma scintigraphic studies for colonic drug delivery in healthy human volunteers. RESULTS: The tablets containing 99mTc-DTPA did not release the tracer in stomach and small intestine, and on entering the colon disintegrated completely whereas the tablets containing 99mTc-SC remained intact in stomach, small intestine and in colon as well. The study showed that DTPA is a suitable tagging agent for 99mTc in the evaluation of guar gum based colonic drug delivery systems containing water-soluble drugs. CONCLUSION: In the present investigation guar gum was applied externally as a compression coat over the radiolabelled core. Since the core consisted of water-soluble material (sodium chloride), it is possible that the release of the tracer from the 99mTcDTPA containing formulations is a combined effect of enzymatic action and diffusion of the salt. The failure of disintegration of 99mTc-SC containing formulations might be due to its interference with the disintegration or the part diffusion observed with 99mTc-DTPA cores. The results of the study showed that DTPA is a suitable tagging agent for 99mTc in the evaluation of colonic drug delivery systems containing water-soluble drugs by gamma scintigraphy. INTRODUCTION Gamma Scintigraphy is a valuable tool in the development and evaluation of pharmaceutical dosage forms. This noninvasive technique gives information in terms of the transit times of oral dosage forms across the different regions of gastrointestinal tract (1), the time and site of disintegration of dosage forms (2) and also the effect of food, disease and size of the formulation on the in vivo performance of the dosage forms. It has become a common practice to evaluate the in vivo performance of novel drug delivery systems in healthy volunteers or patients using scintigraphic technique (3,4). Gamma scintigraphy is found to be particularly useful for the evaluation of colon-specific drug delivery systems. This technique has been used for the evaluation of in vivo behaviour of colonic delivery systems based on pH dependent polymers (5), pectins (6) and guar gum (7). Technetium-99m is the most widely used radionuclide in gamma scintigraphy because of its short halflife, low energy and ready availability. Other radionuclides used are indium-111 (8), samarium-153 (7), etc. The radionuclides are usually ligated with different tagging agents such as diethylene triamine pentaacetic acid (DTPA), sulphur colloid (SC), methylene di-phosphate and pyrophosphate depending on the organ of imaging. Of all these tagging agents, DTPA and SC are routinely used for imaging in nuclear medicine. In majority of the gamma scintigraphic studies involving the evaluation of in vivo behaviour of oral dosage forms, either technetium-99m or indium-111 are ligated with DTPA. In one study 99mTcsulphur colloid (99mTc-SC) was used as a tracer to correlate the in vivo position of the formulation in the gastrointestinal tract with absorption of drug (9). In another study 153Sm was used as a tracer for the pharmacoscintigraphic evaluation of guar gum formulations meant for colonic delivery of dexamethasone (7). In the present investigation, the suitability of 99mTc-DTPA and 99mTc-SC as tracers for the in vivo evaluation of guar gum based colonic delivery systems was studied in healthy volunteers using gamma Corresponding Author: Y.S.R. Krishnaiah, Associate Professor, Department of Pharmaceutical Sciences, Andhra University, Visakhapatnam-530 003, India. [email protected] J Pharm Pharmaceut Sci (www.ualberta.ca/~csps) 5(1):24-28, 2002