title: Spray-dried solid dispersions of nifedipine and vinylcaprolactam/vinylacetate/PEG₆₀₀₀ for compacted oral formulations.
abstract: The aim of this work was to investigate an alternative processing technology for a new polymeric solubilizer used mainly in hot melt extrusion. Poorly soluble nifedipine was co-processed through spray-drying with poly(vinyl caprolactam-co-vinyl acetate-co-ethylene glycol) (PVCVAEG) in different ratios. The resulting spray-dried powders were formulated and compacted into tablets forms. Spray drying produced reduced smooth spherical particles with PVCVAEG and more rough surfaces without PVCVAEG. Crystallinity of the co-processed nifedipine with the polymeric solubilizer was reduced. Plasticization of the polymeric solubilizer was observed with increasing drug content. Diffraction patterns in the small angle region as well as transmission electron microscopy showed results supporting phase separation throughout the spray dried particles of high drug content. Compaction with PVCVAEG improved cohesiveness of spray-dried compacts. Heckel modeling showed that deformation of PVCVAEG containing powders was more plastic compared than brittle nifedipine powders. Dissolution kinetics of all spray-dried samples was improved compared to original nifedipine crystals. Co-processed nifedipine with PVCVAEG did not show improved dissolution rate when compared to spray drying nifedipine alone. All though PVCVAEG is more commonly co-processed with drugs by hot melt extrusion to produce solid dispersions, the results show that it also can be processed by spray drying to produce solid dispersions. PVCVAEG improved compactibility of formulated spray dried powders.
authors.affiliation: Institut Charles Gerhardt - Equipe MACS, UMR 5253, Faculty of Pharmacy, University of Montpellier 1, 15 avenue Charles Flahault, 34093 Montpellier, France.
authors.forename: Ian
authors.initials: I
authors.lastname: Soulairol
authors.affiliation: Institut Charles Gerhardt - Equipe MACS, UMR 5253, Faculty of Pharmacy, University of Montpellier 1, 15 avenue Charles Flahault, 34093 Montpellier, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Tarlier
authors.affiliation: Institut Charles Gerhardt - Equipe MACS, UMR 5253, Faculty of Pharmacy, University of Montpellier 1, 15 avenue Charles Flahault, 34093 Montpellier, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bataille
authors.affiliation: Institut Charles Gerhardt - Equipe MACS, UMR 5253, Faculty of Pharmacy, University of Montpellier 1, 15 avenue Charles Flahault, 34093 Montpellier, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Cacciaguerra
authors.affiliation: Institut Charles Gerhardt - Equipe MACS, UMR 5253, Faculty of Pharmacy, University of Montpellier 1, 15 avenue Charles Flahault, 34093 Montpellier, France. Electronic address: tahmer.sharkawi@univ-montp1.fr.
authors.forename: Tahmer
authors.initials: T
authors.lastname: Sharkawi
mesh_terms: D000284:Administration, Oral; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D009543:Nifedipine / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D033362:Powder Diffraction; D011208:Powders; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D011145:Polyvinyls; D011208:Powders; D013607:Tablets; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D011092:Polyethylene Glycols; D009543:Nifedipine
keywords: Compaction simulator; Drug solubility; Nifedipine; Solid dispersion; Soluplus(®); Spray drying