Wilfried Dr Rer Nat Fischer

Investigation of the Gastrointestinal Transit and In Vivo Drug Release of Isosorbide-5-Nitrate Pellets

An oral formulation of controlled-release isosorbide-5-nitrate pellets has been used to investigate the location of pellets in the gastrointestinal (GI) tract and, in parallel, to measure the drug absorption from these locations. Using the method of gamma scintigraphy the transit times and spreading of pellets in the GI tract have been determined. The method of numeric deconvolution was applied to calculate the drug input into the systemic circulation. The results indicate that a well-absorbed substance such as isosorbide-5-nitrate is absorbed from the stomach and small intestinal in a manner that is controlled by the properties of the pellets. Drug absorption is reduced in the colon. The average transit time from mouth to colon is 6 to 8 hr, which represents the maximum acceptable time for drug release for this oral controlled-release preparation. Taking into account these relations an isosorbide-5-nitrate pellet formulation with a bioavailability of 84% has been developed that maintained the minimal therapeutic plasma level for more than 16 hr after application.

1H-nuclear magnetic resonance (NMR) studies on the inclusion complex of prostaglandin E1 (PGE1) with alpha-cyclodextrin.

Prostaglandin El is currently marketed as a freeze-dried injectable inclusion complex with α-cyclodextrin for the treatment of peripheral arterial diseases. α-Cyclodextrin is used as a stabilizing agent and to improve the dissolution characteristics of prostaglandin El. Upon dilution with the infusion medium, the inclusion complex dissociates almost completely as shown by NMR chemical shift measurements of the complexed and uncomplexed prostaglandin E1 Nuclear Overhauser effect (NOE) measurements of the interacting atoms of α-cyclodextrin and prostaglandin El provide insight into the structure of the complex.