In-Vitrodn-Vivo Correlation of Drug Liberation with an Extended Release Peroral Dosage form for Iloprost in Man

AbstractIloprost is a chemically stable prostacyclin analogue for which therapeutic efficacy was demonstrated after i.v. infusion treatment in several vascular diseases. In order to facilitate drug therapy and to enlarge therapeutic usability an peroral dosage form for non-hospitalized patients was developed on the basis of an extended release (ER) pellet formulation mimicking therapeutic plasma levels as obtained after i.v. infusion in man. Modified drug liberation was pH-independent and showed an in-vitro release of 75 to 95 5% of dose over 3 h at pH 7.4 using the basket method. In 12 PAOD-patients the pharmacokinetic profile of the ER-formulation in capsules (SH K 529 I/M) was characterized after repeated administration of 150 μg iloprost as compared to a standard i.v. infusion treatment with iloprost (Ilomedin®). Peroral treatment resulted in highly reproducible plasma level profiles in the therapeutic range (> 50 pg/ml) for approx. 6 h, i.e. a similar time period as obtained after i.v. infusion. Half...

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