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

TY - JOUR

T1 - Solvent-mediated amorphous-to-crystalline transformation of nitrendipine in amorphous particle suspensions containing polymers

AU - Xia, Dengning

AU - Wu, Jian-Xiong

AU - Cui, Fude

AU - Qu, Haiyan

AU - Rades, Thomas

AU - Rantanen, Jukka

AU - Yang, Mingshi

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012/8/15

Y1 - 2012/8/15

N2 - 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.

AB - 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.

KW - Calcium Channel Blockers

KW - Chemical Precipitation

KW - Chemistry, Pharmaceutical

KW - Crystallization

KW - Crystallography, X-Ray

KW - Kinetics

KW - Microscopy, Polarization

KW - Molecular Structure

KW - Nitrendipine

KW - Phase Transition

KW - Polyethylene Glycols

KW - Polyvinyl Alcohol

KW - Powder Diffraction

KW - Solvents

KW - Spectrum Analysis, Raman

KW - Technology, Pharmaceutical

KW - Water

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1016/j.ejps.2012.03.008

DO - 10.1016/j.ejps.2012.03.008

M3 - Journal article

C2 - 22484330

SN - 0928-0987

VL - 46

SP - 446

EP - 454

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

IS - 5

ER -