Polymer-mediated anti-solvent crystallization of nitrendipine: Monodispersed spherical crystals and growth mechanism

TY - JOUR

T1 - Polymer-mediated anti-solvent crystallization of nitrendipine: Monodispersed spherical crystals and growth mechanism

AU - Xia, Dengning

AU - Ouyang, Mei

AU - Wu, Jian-Xiong

AU - Jiang, Yanbo

AU - Piao, Hongyu

AU - Sun, Shaoping

AU - Zheng, Li

AU - Rantanen, Jukka

AU - Cui, Fude

AU - Yang, Mingshi

PY - 2012/1

Y1 - 2012/1

N2 - Purpose: To investigate anti-solvent crystallization and growth mechanism of nitrendipine spherical crystals in an aqueous solution containing polymeric additives. Methods: Size and shape of crystals were investigated using laser diffractometry, optical microscopy and scanning electron microscopy (SEM). Crystalline form was determined by X-ray powder diffractometer (XRPD). During crystal growth, morphological changes at different time points were observed using SEM. Results: Morphology of nitrendipine crystals was affected by polymers and temperature. Monodispersed micro-spherical crystals were obtained when polyvinyl alcohol (PVA) and PEG 200 were present in crystallization medium at 2°C. During crystallization, large number of amorphous nanoparticles was first observed, followed by aggregation into a core for spherical crystals. Once crystalline state was achieved, rapid growth on core surface was observed with amorphous particles acting as a reservoir allowing formation of star-like particles with needle-like subunits. Spherical crystals were formed by filling the gap between needle-like distinct crystalline units of star-like templates with molecules from dissolved amorphous particles. Conclusions: Monodispersed nitrendipine spherical crystals were obtained using carefully controlled conditions. A mechanism for the nitrendipine spherical crystal growth is suggested. These findings provide a new insight into spherulitic crystallization of active pharmaceutical ingredients.

AB - Purpose: To investigate anti-solvent crystallization and growth mechanism of nitrendipine spherical crystals in an aqueous solution containing polymeric additives. Methods: Size and shape of crystals were investigated using laser diffractometry, optical microscopy and scanning electron microscopy (SEM). Crystalline form was determined by X-ray powder diffractometer (XRPD). During crystal growth, morphological changes at different time points were observed using SEM. Results: Morphology of nitrendipine crystals was affected by polymers and temperature. Monodispersed micro-spherical crystals were obtained when polyvinyl alcohol (PVA) and PEG 200 were present in crystallization medium at 2°C. During crystallization, large number of amorphous nanoparticles was first observed, followed by aggregation into a core for spherical crystals. Once crystalline state was achieved, rapid growth on core surface was observed with amorphous particles acting as a reservoir allowing formation of star-like particles with needle-like subunits. Spherical crystals were formed by filling the gap between needle-like distinct crystalline units of star-like templates with molecules from dissolved amorphous particles. Conclusions: Monodispersed nitrendipine spherical crystals were obtained using carefully controlled conditions. A mechanism for the nitrendipine spherical crystal growth is suggested. These findings provide a new insight into spherulitic crystallization of active pharmaceutical ingredients.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1007/s11095-011-0522-6

DO - 10.1007/s11095-011-0522-6

M3 - Journal article

C2 - 21748536

SN - 0724-8741

VL - 29

SP - 158

EP - 169

JO - Pharmaceutical Research

JF - Pharmaceutical Research

ER -