Polymer-mediated anti-solvent crystallization of nitrendipine: monodispersed spherical crystals and growth mechanism.
Pharm Res
; 29(1): 158-69, 2012 Jan.
Article
en En
| MEDLINE
| ID: mdl-21748536
ABSTRACT
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
/
Bloqueadores de los Canales de Calcio
/
Nitrendipino
/
Composición de Medicamentos
Idioma:
En
Revista:
Pharm Res
Año:
2012
Tipo del documento:
Article
País de afiliación:
China