title: Physicochemical characterization of felodipine-kollidon VA64 amorphous solid dispersions prepared by hot-melt extrusion.
abstract: 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.
authors.affiliation: 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.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China.
authors.forename: Lianyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China. Electronic address: pyang@suda.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.affiliation: Crystal Pharmatech, Suzhou Industrial Park, Suzhou 215123, China.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Wenslow
authors.affiliation: Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tan
authors.affiliation: Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China. Electronic address: hlzhang2008@sinano.ac.cn.
authors.forename: Hailu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China.
authors.forename: Zongwu
authors.initials: Z
authors.lastname: Deng
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry*; D003460:Crystallization; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D015736:Felodipine / Q000737:chemistry*; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy; D010592:Pharmaceutic Aids / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D010592:Pharmaceutic Aids; D011205:Povidone; D015736:Felodipine