Structure, characterization, solubility and stability of podophyllotoxin polymorphs

Abstract

Podophyllotoxin (PPT) is a non-alkaloid toxin lignin with pronounced biological activity. While, solid-state investigation on this active pharmaceuticals ingredient (API) is less concerned. In this contribution, polymorph screening was performed and two anhydrous forms, one hydrate of PPT were harvested, and amorphous PPT was also prepared. These four solid forms were characterized by X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. And their mutual transformation were also disclosed. Form I and II were the stable crystal forms, hydrate was the metastable form, and amorphous polymorph was the unstable form. Form I, II and hydrate could be transformed to amorphous form after heating at 190 °C for 2 h and then quench cooling down to room temperature. The dissolution properties of these forms were also investigated. Form II demonstrated the best solubility and amorphous polymorph showed the fastest intrinsic dissolution rate. The solid-state information of PPT obtained here provided valuable supporting for its further pharmaceutical application and quality control.