SQ-33600

Serum albumin was used as the chiral eluent in combination with achiral liquid chromatog. columns to resolve the enantiomers of and HMG CoA reductase inhibitor and cholesterol-lowering drug, SQ-33600.Satisfactory chiral resolution was achieved by using bovine serum albumin in combination with a Chromegabond di-Me (C-2) column.Resolution required addition of acetonitrile when using horse albumin as the chiral selector.

Humidity-dependent changes in the crystal properties of the disodium salt of a new HMG-CoA reductase inhibitor (SQ-33600, I) were characterized using a combination of gravimetric, thermal, and spectral techniques.The drug substance was found to exhibit rapid moisture sorption and/or desorption, depending on the environmental conditions.Three crystalline solid hydrates and one liquid crystalline phase were identified, each having a definite stability over a range of humidity.The drug substance turned amorphous upon wet granulation, and the amorphous phase reconverted to crystalline hydrates upon exposure to 33-75% relative humidity.To avoid phys. instability of dosage forms due to phase changes, manufacturing of solid dosage forms by dry processing below 52% relative humidity was recommended.The dissolution of drug from solid dosage forms was observed to be independent of the crystal form of the active.