Klaus Nagels

In vitro and in vivo release of estradiol from an intra-muscular microsphere formulation

In vitro 17β-estradiol release from controlled-release microspheres intended for intra-muscular administration was investigated using a rotating bottle apparatus. Prior to intra-muscular administration of 17β-estradiol loaded microspheres the in vivo pharmacokinetics of 17β-estradiol in NZW rabbits were determined: the clearance value was 50.0 ± 8.1 l/d/kg and the elimination half-life was 7.7 ± 2.2 min (n = 6 ± S.D.). The release of 17β-estradiol from the microspheres in vivo was determined and compared to the release profile obtained in vitro using two release protocols. There was a linear relationship from day 0 until day 30 irrespective of which in vitro test protocol was used. It is suggested that the rotating bottle apparatus is a good starting point for the development of an in vitro release test method for controlled-released intra-muscular dosage forms. Possible strategies for the improvement of an in vitro test to predict in vivo release are discussed.