Two new polymorphs and one dihydrate of lenalidomide: solid-state characterization study

2019-07-22T09:46:40Z (GMT) by Lina Jia Zhonghua Li Junbo Gong

Purpose: Lenalidomide (LDM) is a blockbuster drug for multiple myeloma and non-Hodgkin’s lymphoma, and contributed $ 6.974 billion in sales for Celgene in 2016. The aim of this research is to expand the crystal form landscape, characterize the physicochemical properties and thoroughly investigate the potential solid forms transformation for this famous drug.

Materials and methods: In this study, a comprehensive solid-state screening was carried out. The physicochemical properties, stability and phase transformation were fully investigated using powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), solid state nuclear magnetic resonance (solid state NMR) and Infrared Spectroscopic Analysis (IR). Finally the differences of dissolution behavior were compared through powder dissolution test.

Results: Two new anhydrous forms (α and β) and one new dihydrate form (DH) of LDM were discovered through a comprehensive solid-state screening experiment. The new discovered DH showed better stability under accelerated storage condition (40 °C/75% RH) and in most organic solvents than other forms. The new discovered form α exhibited faster dissolution rate in the early phase and larger apparent solubility than the currently marketed form.

Conclusions: These new forms exhibit a new chance for drug development in view of their pharmaceutical properties and intellectual property.