Physicochemical characterization of felodipine-kollidon VA64 amorphous solid dispersions prepared by hot-melt extrusion. 2013

Yuejun Song, and Lianyan Wang, and Ping Yang, and Robert M Wenslow, and Bo Tan, and Hailu Zhang, and Zongwu Deng
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.

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.

UI MeSH Term Description Entries
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D010592 Pharmaceutic Aids Substances which are of little or no therapeutic value, but are necessary in the manufacture, compounding, storage, etc., of pharmaceutical preparations or drug dosage forms. They include SOLVENTS, diluting agents, and suspending agents, and emulsifying agents. Also, ANTIOXIDANTS; PRESERVATIVES, PHARMACEUTICAL; COLORING AGENTS; FLAVORING AGENTS; VEHICLES; EXCIPIENTS; OINTMENT BASES. Aids, Pharmaceutic,Aids, Pharmaceutical,Pharmaceutical Aids
D011205 Povidone A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander. Polvidone,Polyvidon,Polyvinylpyrrolidone,Arufil,Bolinan,Bolinan 40,Crospovidone,Dulcilarmes,Duratears Free,Enterodes,Enterodez,Hypotears,Kollidon,Lacophtal,Lacri-Stulln,Lagrifilm,Liquifilm Lagrimas,Nutrivisc,Oculotect,PVP 40,Periston,Plasdone,Polyplasdone XL,Povidone, Unspecified,Protagens,Protagent,Unifluid,Vidirakt S mit PVP,Vidisic PVP Ophtiole,Wet-Comod,Dulcilarme,Enterode,Hypotear,Polyvidons,Protagen,Unspecified Povidone
D003460 Crystallization The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Crystalline Polymorphs,Polymorphism, Crystallization,Crystal Growth,Polymorphic Crystals,Crystal, Polymorphic,Crystalline Polymorph,Crystallization Polymorphism,Crystallization Polymorphisms,Crystals, Polymorphic,Growth, Crystal,Polymorph, Crystalline,Polymorphic Crystal,Polymorphisms, Crystallization,Polymorphs, Crystalline
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D004355 Drug Stability The chemical and physical integrity of a pharmaceutical product. Drug Shelf Life,Drugs Shelf Lives,Shelf Life, Drugs,Drug Stabilities,Drugs Shelf Life,Drugs Shelf Live,Life, Drugs Shelf,Shelf Life, Drug,Shelf Live, Drugs,Shelf Lives, Drugs
D006358 Hot Temperature Presence of warmth or heat or a temperature notably higher than an accustomed norm. Heat,Hot Temperatures,Temperature, Hot,Temperatures, Hot
D000959 Antihypertensive Agents Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. Anti-Hypertensive,Anti-Hypertensive Agent,Anti-Hypertensive Drug,Antihypertensive,Antihypertensive Agent,Antihypertensive Drug,Anti-Hypertensive Agents,Anti-Hypertensive Drugs,Anti-Hypertensives,Antihypertensive Drugs,Antihypertensives,Agent, Anti-Hypertensive,Agent, Antihypertensive,Agents, Anti-Hypertensive,Agents, Antihypertensive,Anti Hypertensive,Anti Hypertensive Agent,Anti Hypertensive Agents,Anti Hypertensive Drug,Anti Hypertensive Drugs,Anti Hypertensives,Drug, Anti-Hypertensive,Drug, Antihypertensive,Drugs, Anti-Hypertensive,Drugs, Antihypertensive
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D014961 X-Ray Diffraction The scattering of x-rays by matter, especially crystals, with accompanying variation in intensity due to interference effects. Analysis of the crystal structure of materials is performed by passing x-rays through them and registering the diffraction image of the rays (CRYSTALLOGRAPHY, X-RAY). (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Xray Diffraction,Diffraction, X-Ray,Diffraction, Xray,Diffractions, X-Ray,Diffractions, Xray,X Ray Diffraction,X-Ray Diffractions,Xray Diffractions

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