AbstractsBiology & Animal Science

The aim of this work was to investigate suitable intramuscularly and in particular subcutaneously injectable drug delivery systems for steroids. First, drospirenone (DRSP) microcrystal suspensions (MCS) and DRSP organogels were studied with focus on the physicochemical stability and applicability. Advantageously, DRSP provided high chemical stability in oils. Because DRSP was insufficiently soluble in the tested oils, oil-based DRSP MCS were analyzed as possible formulation options. The physical stability of oil-based DRSP MCS was increased with the addition of suitable excipients; especially silica derivatives showed a positive impact. Moreover, the addition of organogelators improved the physical stability of the MCS. DRSP organgogels were completely stable against sedimentation during storage. Furthermore, organogelators significantly reduced particle size growth. Due to gel destruction by mechanical stress, ejection of DRSP organogels was still possible using an autoinjector. Moreover, the organogels exhibited significantly slower DRSP release than non-stabilized MCS. In addition, the pharmacokinetics of steroids, in particular DRSP and ZK28, which were incorporated into injectable carrier systems, was analyzed. Aqueous DRSP MCS showed slower absorption profiles than oil-based DRSP MCS. Conspicuously high initial serum peaks characterized the pharmacokinetics of aqueous and in particular oil-based DRSP MCS. Moreover, aqueous MCS exhibited significantly lower AUCs than oil-based MCS in rats, possibly due to too slow dissolution of lipophilic DRSP in the subcutaneous tissue after fast diffusion of the aqueous vehicle. Since oils stay longer at the injection site, the risk of residual drug after vehicle diffusion is lower. Oil-based ZK28 preparations and ZK28 organogels provided high initial plasma levels as well. Over the later course, ZK28 organogels advantageously exhibited more constant drug plasma levels and significantly higher AUCs than oil-based ZK28 formulations, most likely due to the partial restructure of gel network that was shown in rheological tests. Overall, organogels were evaluated as promising carrier system for steroids. Finally, the ability to combine DRSP and ethinyl estradiol (EE) delivery systems and the in vitro release of the combined systems were studied. The EE poly(lactide-co-glycolide) PLGA and poly(butylcyanoacrylate) microparticles and DRSP PLGA microspheres were combinable in an aqueous vehicle without interfering each other. DRSP PLGA microparticles did not show an initial burst effect and provided more sustained drug release than EE microparticles. Overall, PLGA microparticles were evaluated as suitable depot systems for DRSP. Advantageously, EE PLGA microparticles incorporated in DRSP organogel showed significantly slower drug release than the aqueous EE PLGA microparticles dispersion. The combined EE and DRSP system was evaluated as suitable for the simultaneous sustained release of both drugs. Ziel der Arbeit war es, intramuskulär und insbesondere subkutan injizierbare…