College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China; Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China.
Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China.
J Pharm Sci. 2013 Jun;102(6):1915-1923. doi: 10.1002/jps.23538. Epub 2013 Apr 11.
To improve the dissolution and hence the oral bioavailability, amorphous felodipine (FEL) solid dispersions (SDs) with Kollidon® VA 64 (PVP/VA) were prepared. Hot-melt extrusion was employed with an extruding temperature below the melting point (Tm ) of FEL. X-ray powder diffraction (XRPD) and (13) C CP/MAS nuclear magnetic resonance (NMR) measurements show that the extrudates are amorphous. The intermolecular interaction between FEL and PVP/VA in SDs was investigated by Fourier transform infrared spectroscopy, (15) N CP/MAS NMR, and (1) H high-resolution MAS NMR. Furthermore, a single glass transition temperature (Tg ) was detected by differential scanning calorimetry in addition to a single (1) H T1 or T1rho relaxation time detected by (13) C NMR signals. These results confirm that the extrudates contain FEL dispersed into the polymer matrix at a molecular level with no detectable phase separation. This molecular-scale mixing results in a significantly faster dissolution rate compared with the pure crystalline FEL. Additionally, the molecular-scale mixing prevents the amorphous drug from recrystallizing even after being stored at 40°C/75% Relative Humidity for 2 months.
为了提高溶解速度，从而提高口服生物利用度，将无定形非洛地平（FEL）与共聚维酮（PVP/VA）制成固体分散体（SD）。采用熔融挤出法，挤出温度低于 FEL 的熔点（Tm）。X 射线粉末衍射（XRPD）和（13）C CP/MAS 核磁共振（NMR）测量表明挤出物为无定形。通过傅里叶变换红外光谱、（15）N CP/MAS NMR 和（1）H 高分辨率 MAS NMR 研究了 SD 中 FEL 和 PVP/VA 之间的分子间相互作用。此外，差示扫描量热法检测到单一玻璃化转变温度（Tg），此外，（13）C NMR 信号检测到单一（1）H T1或 T1rho 弛豫时间。这些结果证实挤出物包含分散在聚合物基质中的 FEL，达到分子水平，没有检测到相分离。这种分子级混合导致与纯结晶 FEL 相比，溶解速度显著加快。此外，即使在 40°C/75%相对湿度下储存 2 个月后，分子级混合也能防止无定形药物再结晶。
