Forced degradation studies of rapamycin: identification of autoxidation products.

The immunosuppressant drug rapamycin, also known as Sirolimus, underwent autoxidation under mild conditions to give numerous monomeric and oligomeric compounds, which were generally characterized by size-exclusion chromatography and NP-HPLC with UV and MS detection. Some of the more predominant products, epoxides and ketones, were isolated and identified. Two epoxides and 10S-epimer of rapamycin were described for the first time.

Investigation of the effects of pharmaceutical processing upon solid-state NMR relaxation times and implications to solid-state formulation stability.

Crystalline lactose was subjected to various forms of pharmaceutical processing including compaction, lyophilization, spray drying, and cryogrinding. (13)C cross polarization and magic-angle spinning (CPMAS) NMR spectra were acquired for bulk crystalline lactose as well as the processed samples. Saturation recovery experiments to determine proton spin-lattice relaxation times ((1)H T(1)) showed that the alpha-monohydrate form had a (1)H T(1) of 243 s, while compaction resulted in a threefold reduction in T(1) (79 s), with little change in the spectrum.