title: Evaluation of the in vitro release and pharmacokinetics of parenteral injectable formulations for steroids.
abstract: The aim of this study was to investigate the pharmacokinetics of injectable conventional dosage forms containing steroids. First, the in vitro release of drospirenone (DRSP) microcrystal suspensions (MCSs) was studied. Next, the pharmacokinetics of selected subcutaneously injected DRSP MCSs was analyzed in female Wistar rats and Cynomolgus monkeys. Furthermore, in vivo and in vitro results were fitted to mathematical models. Although the in vitro-in vivo correlation was partially good, the predictability of the in vitro test was assumed to be restricted. Nevertheless, mathematical calculations and in vitro results allow the interpretation of in vivo results and the identification of parameters influencing the drug release. DRSP microcrystal size had a marginal influence on the pharmacokinetics. The drug absorption was slower from aqueous MCSs than from peanut oil MCSs. Absorption profiles of aqueous DRSP MCSs correlated best with Hixson-Crowell model, whereas absorption profiles of oil-based DRSP MCSs showed a good fit to the Higuchi model. The established assumptions were used to interpret the pharmacokinetics of subcutaneously injected oil-based formulations of the steroid ZK28. In summary, low drug solubility in the vehicle and a high vehicle viscosity were assumed to result in slower and constant drug release.
authors.affiliation: Pharmaceutical Technology, Bayer HealthCare Pharmaceuticals, Berlin, Germany. Electronic address: stefanie.nippe@googlemail.com.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nippe
authors.affiliation: Drug Metabolism and Pharmacokinetics, Bayer HealthCare Pharmaceuticals, Berlin, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Preuße
authors.affiliation: Pharmaceutical Technology, Bayer HealthCare Pharmaceuticals, Berlin, Germany.
authors.forename: Sascha
authors.initials: S
authors.lastname: General
mesh_terms: D000736:Androstenes / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004304:Dosage Forms; D005260:Female; D007267:Injections; D008252:Macaca fascicularis; D009821:Oils / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013535:Suspensions / Q000008:administration & dosage / Q000493:pharmacokinetics; D014783:Viscosity
chemical_list: D000736:Androstenes; D004304:Dosage Forms; D009821:Oils; D013535:Suspensions; C035144:drospirenone
keywords: 17β-Hydroxysteroid dehydrogenase inhibitor; Drospirenone; Hormone; Microcrystal suspension; Organogel; Subcutaneous