title: Solvent-mediated amorphous-to-crystalline transformation of nitrendipine in amorphous particle suspensions containing polymers.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors.forename: Dengning
authors.initials: D
authors.lastname: Xia
authors.forename: Jian X
authors.initials: JX
authors.lastname: Wu
authors.forename: Fude
authors.initials: F
authors.lastname: Cui
authors.forename: Haiyan
authors.initials: H
authors.lastname: Qu
authors.forename: Thomas
authors.initials: T
authors.lastname: Rades
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
authors.forename: Mingshi
authors.initials: M
authors.lastname: Yang
mesh_terms: D002121:Calcium Channel Blockers / Q000737:chemistry*; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D007700:Kinetics; D008859:Microscopy, Polarization; D015394:Molecular Structure; D009568:Nitrendipine / Q000737:chemistry*; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D033362:Powder Diffraction; D012997:Solvents / Q000737:chemistry*; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry
chemical_list: D002121:Calcium Channel Blockers; D012997:Solvents; D014867:Water; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D009568:Nitrendipine