Nycomed Pharma

Hydrogenolysis of alkyl azides I (n = 3, 4, 5) with palladium on carbon and hydrogen followed by acylation with with benzyloxycarbonyl chloride gives the protected sym. secondary amines II.E.g., reduction of I (n = 4) with 5% Pd/C and H₂ in EtOH followed by treatment with PhCH₂OCOCl and NaHCO₃ solution gives 63% of the protected amine II (n = 3).

Stereoselective syntheses of hydroxylated azalkene-α,α'-bridged bis(α-glycine) derivative I (Z = CO₂CH₂Ph, Fmoc = 9-fluorenylmethoxycarbonyl) and lysine derivative II are described.The bridge was formed as a secondary amine by a reductive dimerization process of two azide mols. upon hydrogenolysis over 5% palladium-on-charcoal.Lysine derivatives were formed by reduction of the azide function to a primary amine.

Dissolution stability is evaluated on three multiparticulate membrane controlled-release tablet formulations.The evaluation is based on anal. of the parameters in the Order Model that is used to characterize the dissolution profiles.By a simple statistical-graphical approach, the change during storage is evaluated, and mechanisms likely to be responsible for instability are identified.The method is more sensitive than the classical evaluation of dissolution data in fixed points.A high-stress condition (50°C/ambient humidity in 10-21 days) was used to make the tablets unable to disintegrate.Dissolution profiles from these tablets were fitted to the Order Model thus showing how the parameters are affected by slow and incomplete disintegration.This knowledge facilitated interpretation of 40°C storage data as the observed effects could be differentiated into disintegration-related and release mechanism-related.For the three tested products, the stability anal. showed that the disintegration properties play a predominant role for the dissolution stability.