CHARACTERIZATION OF HUMIDITY-DEPENDENT CHANGES IN CRYSTAL PROPERTIES OF A NEW HMG-COA REDUCTASE INHIBITOR IN SUPPORT OF ITS DOSAGE FORM DEVELOPMENT

Humidity-dependent changes in the crystal properties of the disodium salt of a new HMG-CoA reductase inhibitor (SQ-33600) 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 physical 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.