One-month sustained release microspheres of 125I-bovine calcitonin -: In vitro in vivo studies

To obtain a 1-month release formulation of I-125-bovine calcitonin, microspheres were prepared with three different PLA copolymers, PLGA I (mol. wt. [MW]=30 000), polyethyleneglycol (PEG)-PLGA (MW=34 000) and PLGA II (MW=12 000) using the double emulsion method. The release of I-125-bovine calcitonin was assayed in vitro using dialysis bags at 37 degrees C in isotonic phosphate buffer (pH 7.4). The in vitro release results indicated a very slow release rate for an optimal 1-month sustained release formulation. I-125-bovine calcitonin microspheres were administered under the skin on the back of Wistar rats and the radioactivity at the injection site was subsequently measured over a 4-week period. The in vitro and in vivo profiles were affected by the weight average molecular weight of the copolymers. The I-125-bovine calcitonin release rate was faster from microspheres prepared with PLGA II (MW=12 000) than from microspheres prepared with higher molecular weight copolymers (PLGA I and PEG-PLGA). Microspheres prepared with PLGA II (MW=12 000) release 100% of the dose in 1 month, in vivo release profiles presented two phases, during the first 2 weeks approximately 70% of the I-125-bovine calcitonin injected was released, followed by a second slower phase. (C) 1999 Published by Elsevier Science B.V. All rights reserved.