title: Formulation of poorly water-soluble drugs via coacervation--a pilot study using febantel.
abstract: In this study, febantel was dissolved under increased temperature in a nonionic surfactant Lutrol L44® and subsequently mixed into an aqueous maltodextrin solution. After 8h under static conditions, coacervation or phase separation took place. (1)H NMR spectra and HPLC analysis showed that the upper phase contained mainly all febantel, while no febantel was detected in the lower phase. Fluorescent microscopy showed that maltodextrin is distributed in the lower phase. Coacervation proved to be a promising formulation technology for certain poorly water-soluble drugs, such as febantel. The coacervate phase showed an increase in in vitro dissolution kinetics, compared to Rintal® granules. These results were confirmed in an in vivo study performed on dogs. Febantel and fenbendazole showed a significant increase in plasma concentration compared to Rintal® granules. Further studies have to be performed to transform coacervates into a solid dosage form and to prove broad applicability to other poorly soluble drugs.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: De Jaeghere
authors.forename: B G
authors.initials: BG
authors.lastname: De Geest
authors.forename: J
authors.initials: J
authors.lastname: Van Bocxlaer
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
authors.forename: A
authors.initials: A
authors.lastname: Antunes da Fonseca
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001562:Benzimidazoles / Q000138:chemical synthesis; D001702:Biopharmaceutics / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D015195:Drug Design; D005273:Fenbendazole / Q000138:chemical synthesis; D006146:Guanidines / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D001562:Benzimidazoles; D006146:Guanidines; C506200:Lutrol; D013501:Surface-Active Agents; D014867:Water; D011092:Polyethylene Glycols; D005273:Fenbendazole; C011030:oxfendazole; C017309:febantel
keywords: Coacervation; Febantel; Lutrol; Nonionic tensioactive agent; Phase separation; Poorly water-soluble drugs