title: Polymer-mediated anti-solvent crystallization of nitrendipine: monodispersed spherical crystals and growth mechanism.
abstract: OBJECTIVE
  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.
authors: Department of Pharmaceutics, School of Pharmaceutical Science, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China.
authors: Dengning
authors: D
authors: Xia
authors: Mei
authors: M
authors: Ouyang
authors: Jian X
authors: JX
authors: Wu
authors: Yanbo
authors: Y
authors: Jiang
authors: Hongyu
authors: H
authors: Piao
authors: Shaoping
authors: S
authors: Sun
authors: Li
authors: L
authors: Zheng
authors: Jukka
authors: J
authors: Rantanen
authors: Fude
authors: F
authors: Cui
authors: Mingshi
authors: M
authors: Yang
mesh_terms: D002121:Calcium Channel Blockers / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D008855:Microscopy, Electron, Scanning; D009568:Nitrendipine / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D012997:Solvents; D013696:Temperature; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D002121:Calcium Channel Blockers; D011108:Polymers; D012996:Solutions; D012997:Solvents; D014867:Water; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol; D009568:Nitrendipine