Quality management system and accreditation of the in vivo monitoring laboratory at Karslruhe Institute of Technology.

The in vivo monitoring laboratory (IVM) at Karlsruhe Institute of Technology (KIT), with one whole body counter and three partial-body counters, is an approved lab for individual monitoring according to German regulation. These approved labs are required to prove their competencies by accreditation to ISO/IEC 17025:2005. In 2007 a quality management system (QMS), which was successfully audited and granted accreditation, was set up at the IVM.

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

Prostaglandin E1 is currently marketed as a freeze-dried injectable inclusion complex with alpha-cyclodextrin for the treatment of peripheral arterial diseases. alpha-Cyclodextrin is used as a stabilizing agent and to improve the dissolution characteristics of prostaglandin E1. 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.

[Development of tolerance in continuous nitroglycerin infusion].

For treatment of unstable angina pectoris or recent myocardial infarction, intravenous NTG is frequently employed, beginning with doses of 3 mg/h or more; thereafter, dependent on the clinical course, in particular, if the blood pressure is lowered notably, the dose may be reduced to 1 or 2 mg/h. Reports published in recent years have documented to the development of tolerance to nitrates when given orally in higher doses three times daily or administered by the transdermal mode. Accordingly, we suspected that tolerance development would be the inevitable outcome during a continuous intravenous infusion of NTG.

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.

Isosorbide-5-nitrate sustained-release pellets - an example of computer-supported drug development.

To achieve a fast onset and a sufficiently long duration of action in the long-term treatment of angina pectoris a composite dosage form was developed, consisting of a fast-release initial dose Di and a slow-release maintenance dose Dm. The product is designed to be given once daily in the morning to achieve sufficiently high blood levels for clinical response during day-time with declining blood levels during night-time to avoid tolerance. In view of its pharmacokinetic properties, the antianginal drug isosorbide-5-nitrate (IS-5-N) was selected as the model substance.