IN-VITRO AND IN-VIVO RELEASE OF ESTRADIOL FROM ART INTRA-MUSCULAR MICROSPHERE FORMULATION

In vitro 17 beta-estradiol release from controlled-release microsphere s intended for intra-muscular administration was investigated using a rotating bottle apparatus. Prior to intra-muscular administration of 1 7 beta-estradiol loaded microspheres the in vivo pharmacokinetics of 1 7 beta-estradiol in NZW rabbits were determined: the clearance value w as 50.0+/-8.1 1/d/kg and the elimination half-life was 7.7+/-2.2 min ( n=6+/-S.D.). The release of 17 beta-estradiol from the microspheres in vivo was determined and compared to the release profile obtained in v itro using two release protocols. There was a linear relationship from day 0 until day 30 irrespective of which in vitro test protocol was u sed. It is suggested that the rotating bottle apparatus is a good star ting point for the development of an in vitro release test method for controlled-released intra-muscular dosage forms. Possible strategies f or the improvement of an in vitro test to predict in vivo release are discussed. (C) 1997 Elsevier Science B.V.