title: The use of a new hydrophilic polymer, Kollicoat IR, in the formulation of solid dispersions of Itraconazole.
abstract: Kollicoat IR, a new pharmaceutical excipient developed as a coating polymer for instant release tablets, was evaluated as a carrier in solid dispersions of Itraconazole. The solid dispersions were prepared by hot stage extrusion. Modulated temperature differential scanning calorimetry and X-ray powder diffraction were used to evaluate the miscibility of the drug and the carrier. The pharmaceutical performance was evaluated by dissolution experiments, performed in simulated gastric fluid without pepsin (SGF(sp)). In the X-ray diffractograms no Itraconazole peaks were visible; the polymer on the other hand appeared to be semi-crystalline. Moreover, its crystallinity increased during the extrusion process due to exposure to heat and shear forces. Modulated temperature differential scanning calorimetry analysis showed that the drug and the polymer formed a two phase system. Separate clusters of glassy Itraconazole were present for drug loads of 40% or higher, indicating further phase separation. Dissolution measurements demonstrated a significantly increased dissolution rate for the solid dispersions compared to physical mixtures. Interestingly the physical mixture made up of glassy Itraconazole and Kollicoat IR (20/80, w/w) showed a dissolution rate and maximum that was much higher than that of the physical mixture made up of crystalline Itraconazole and that of pure glassy Itraconazole. The results of this study show that Kollicoat IR is a promising excipient for the formulation of solid dispersions of Itraconazole prepared by hot stage extrusion.
authors.affiliation: Laboratorium voor Farmacotechnologie en Biofarmacie, K.U.Leuven, Leuven, Belgium.
authors.forename: Sandrien
authors.initials: S
authors.lastname: Janssens
authors.forename: Hector Novoa
authors.initials: HN
authors.lastname: de Armas
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Guy
authors.initials: G
authors.lastname: Van den Mooter
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D017964:Itraconazole / Q000008:administration & dosage* / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013607:Tablets; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000935:Antifungal Agents; D005079:Excipients; C519734:Kollicoat IR; D011145:Polyvinyls; D013607:Tablets; D017964:Itraconazole