EFFECT OF SURFACTANT AGENTS ON THE RELEASE OF I-125 BOVINE CALCITONINFROM 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 a nd in vivo. The release of I-125-bovine calcitonin was determined in v itro at 37 degrees C in isotonic phosphate buffer (pH 7.4). I-125-bovi ne calcitonin microspheres (5 mg) were administered under the skin on the back of Wistar rats and the radioactivity at the injection site wa s subsequently measured over a 6-week period. The in vivo and in vitro I-125-bovine calcitonin profiles were affected by the surfactant agen ts, but in vivo release was much faster than in vitro. Following injec tion in rats, microspheres made with Tween(R)-80 and Span(R)-60 to giv e a hydrophile-lypophile balance (HLB) value of 6 and 8 in the first e mulsion, 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) respective ly. Under these conditions, they take 8 and 10 weeks, respectively, to release the total amount of calcitonin.