In-vitro and in-vivo evaluation of diclofenac sodium intramuscular injection using gamma scintigraphy

Full text: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which is available as over-the-counter (OTC) medication for the systemic and topical treatment of painful and inflammatory conditions such as arthritis and back pain. This study was undertaken to investigate the distribution and retention of intramuscularly injected diclofenac sodium (DFN) in white New Zealand rabbit using gamma scintigraphy. A new formulation of the nonselective NSAID diclofenac sodium suitable for intramuscular injection has been developed using sesame oil as a vehicle. The hypothesis of present work is to maintain effective concentration of DFN in blood for prolonged time period. A novel method of radiolabeling with 99mTc-pertechnetate was adopted using stannous ions as reducing agent. The radiolabeled product was tested for quality control using ascending instant thin layer chromatography (ITLC) technique. ITLC-SG, (Gelman, USA) and acetone were used as the stationary phase and mobile phase respectively in the chromatographic procedure. In vitro and in vivo stability parameters were evaluated. Biodistribution studies and blood kinetics of 99mTc-DFN was done in balb c mice and white New Zealand rabbit respectively. 99mTc-DFN retention at depot site was evaluated using gamma scintigraphy. 99mTc-DFN, when incubated at 37 deg C for 24 hr in normal saline and human serum showed disintegration of only 6.6% and 3.5% respectively, thereby indicating high stability of radiolabeled product. Protein binding studies of 99mTc-DFN shows more than 85% serum protein binding. Blood clearance of radiopharmaceutical in rabbits, exhibited a biphasic exponential pattern in i.v. bolus while in i.m. linear control release pattern were observed up to 24 hrs