title: Thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.
abstract: This study evaluated thermoplastic polyurethanes (TPUR) as matrix excipients for the production of oral solid dosage forms via hot melt extrusion (HME) in combination with injection molding (IM). We demonstrated that TPURs enable the production of solid dispersions - crystalline API in a crystalline carrier - at an extrusion temperature below the drug melting temperature (Tm) with a drug content up to 65% (wt.%). The release of metoprolol tartrate was controlled over 24h, whereas a complete release of diprophylline was only possible in combination with a drug release modifier: polyethylene glycol 4000 (PEG 4000) or Tween 80. No burst release nor a change in tablet size and geometry was detected for any of the formulations after dissolution testing. The total matrix porosity increased gradually upon drug release. Oral administration of TPUR did not affect the GI ecosystem (pH, bacterial count, short chain fatty acids), monitored via the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The high drug load (65 wt.%) in combination with (in vitro and in vivo) controlled release capacity of the formulations, is noteworthy in the field of formulations produced via HME/IM.
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Claeys
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors.forename: Anouk
authors.initials: A
authors.lastname: Vervaeck
authors.affiliation: Polymer Chemistry Research Group, Department of Organic Chemistry, Ghent University, Ghent, Belgium.
authors.forename: Xander K D
authors.initials: XK
authors.lastname: Hillewaere
authors.affiliation: Laboratory of Microbial Ecology and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
authors.forename: Sam
authors.initials: S
authors.lastname: Possemiers
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors.forename: Laurent
authors.initials: L
authors.lastname: Hansen
authors.affiliation: Laboratory of Pharmaceutical Process Analytical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors.forename: Thomas
authors.initials: T
authors.lastname: De Beer
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium.
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.affiliation: Laboratory of Pharmaceutical Technology, Department of Pharmaceutics, Ghent University, Ghent, Belgium. Electronic address: Chris.Vervaet@UGent.be.
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004304:Dosage Forms; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D004400:Dyphylline / Q000008:administration & dosage / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006358:Hot Temperature; D006801:Humans; D008790:Metoprolol / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011140:Polyurethanes / Q000008:administration & dosage* / Q000737:chemistry*; D016062:Porosity; D013607:Tablets / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004337:Drug Carriers; D005079:Excipients; D011140:Polyurethanes; D013607:Tablets; D004400:Dyphylline; D011092:Polyethylene Glycols; D008790:Metoprolol
keywords: Controlled release; Drug delivery systems; Extrusion; Injection molding; Polymers; Polyurethane