Solvent-mediated amorphous-to-crystalline transformation of nitrendipine in amorphous particle suspensions containing polymers

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Dengning Xia, Jian-Xiong Wu, Fude Cui, Haiyan Qu, Thomas Rades, Jukka Rantanen, Mingshi Yang

The amorphous-to-crystalline transformation of nitrendipine was investigated using Raman spectroscopy and X-ray powder diffraction (XRPD). The nucleation and growth rate of crystalline nitrendipine in a medium containing poly (vinyl alcohol) (PVA) and polyethylene glycol (PEG 200) were quantitatively determined using image analysis based on polarized light microscopy. The findings from the image analysis revealed that the transformation process occurred through the dissolution of amorphous drug precipitate followed by the nucleation and growth of the crystalline phase with the amorphous precipitate acting as a reservoir for maintaining the supersaturation. The rates of nucleation and crystal growth of nitrendipine decreased with an increase in PEG 200 concentration in organic phase from 0% to 75% (v/v). Increasing the PVA concentration in water phase from 0.1% to 1.0% (w/w) also decreased the rates of nucleation and crystal growth, however, an increase in PVA concentration from 1.0% to 2.0% (w/w) did not result in a further decrease in the rates of nucleation and crystal growth. An increase in drug concentrations in the organic phase from 10 mg/ml to 30 mg/ml led to faster nucleation rates. However, a further increase in drug concentration to 100mg/ml decelerated the growth of nitrendipine crystals. Combining image analysis of polarized light micrographs together with Raman spectroscopy and XRPD provided an in-depth insight into solid state transformations in amorphous nitrendipine suspensions.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Pharmaceutical Sciences
Vol/bind46
Udgave nummer5
Sider (fra-til)446-454
Antal sider9
ISSN0928-0987
DOI
StatusUdgivet - 15 aug. 2012

ID: 38145996