Effect of surfactant agents on the release of I-125-bovine calcitonin from PLGA microspheres: In vitro in vivo study.

DL,PLGA-microspheres of I-125-Bovine calcitonin prepared by the double emulsion technique (including Tween(R)-80 in the water phase and Span(R)-60 in the oil phase of the first emulsion) were studied in vitro and in vivo. The release of I-125-bovine calcitonin was determined in vitro at 37 degrees C in isotonic phosphate buffer (pH 7.4). I-125-bovine calcitonin microspheres (5 mg) were administered under the skin on the back of Wistar rats and the radioactivity at the injection site was subsequently measured over a 6-week period. The in vivo and in vitro I-125-bovine calcitonin profiles were affected by the surfactant agents, but in vivo release was much faster than in vitro. Following injection in rats, microspheres made with Tween(R)-80 and Span(R)-60 to give a hydrophile-lypophile balance (HLB) value of 6 and 8 in the first emulsion, released 20 and 14% of the radioactivity within the first 24 h, but only 1.3 and 1.2%/day at later times (up to 6 weeks) respectively. Under these conditions, they take 8 and 10 weeks, respectively, to release the total amount of calcitonin.