title: Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion.
abstract: The aim of the present work was to investigate in vitro dissolution properties of three binary solid solutions prepared by a hot-melt extrusion (HME) process with vinyl pirrolidone--vinyl acetate copolymer (Kollidon VA 64), ethyl acrylate, methyl methacrylate polymer (Eudragit E) polyetilenglicol 8000 (PEG 8000) with a cannabinoid type 1 (CB-1) antagonist. Hansen solubility parameters were calculated from the chemical structures of the drug and the individual polymers in order to predict miscibility. Solid state characterizations of drug substance, physical blends and HME formulations were performed with differential scanning calorimetry. The dissolution testing conducted under sink conditions revealed that the dissolution rate of HME formulations improved around 1.8-fold vs drug substance. Supersaturation dissolution study demonstrated that HME formulations composed by Eudragit E and Kollidon VA64 increased drug solubility between 30- and 35-fold, respectively comparing to the drug substance. Physical and chemical stability of formulations were studied at 40°C/75%HR with open dish during 15 days. The formulation composed by the drug and Eudragit E at 10:90 was evaluated for in vivo drug absorption in male Wistar-Hannover rats and it was found to increase CB-1 absorption threefold greater than pure drug oral suspension.
authors.affiliation: ESTEVE Lab, Pharmaceutical Innovation and Pharmacokinetic department, Poligono Industrial c/Sant Marti, Barcelona, Spain. lsoler@esteve.es
authors.forename: L S
authors.initials: LS
authors.lastname: Ranzani
authors.forename: J
authors.initials: J
authors.lastname: Font
authors.forename: F
authors.initials: F
authors.lastname: Galimany
authors.forename: A
authors.initials: A
authors.lastname: Santanach
authors.forename: A M
authors.initials: AM
authors.lastname: Gomez-Gomar
authors.forename: G
authors.initials: G
authors.lastname: Casadevall
authors.forename: A
authors.initials: A
authors.lastname: Gryczke
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D006358:Hot Temperature; D008297:Male; D008689:Methacrylates / Q000737:chemistry*; D008768:Methylmethacrylates; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D012995:Solubility
chemical_list: D004337:Drug Carriers; D008689:Methacrylates; D008768:Methylmethacrylates; D043884:Receptor, Cannabinoid, CB1; C102808:Eudragit-E; D011092:Polyethylene Glycols; D011205:Povidone