title: Development of sustained and dual drug release co-extrusion formulations for individual dosing.
abstract: In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification.
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany. Electronic address: Julia.Laukamp@hhu.de.
authors.forename: Eva Julia
authors.initials: EJ
authors.lastname: Laukamp
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: An-Katrien
authors.initials: AK
authors.lastname: Vynckier
authors.affiliation: Conexus Pharma, Ghent, Belgium.
authors.forename: Jody
authors.initials: J
authors.lastname: Voorspoels
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Thommes
authors.affiliation: Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Duesseldorf, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Breitkreutz
mesh_terms: D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D006358:Hot Temperature; D012995:Solubility; D013607:Tablets / Q000008:administration & dosage / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*; D013718:Tensile Strength
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D013607:Tablets; D002220:Carbamazepine
keywords: Biphasic drug release; Co-extrusion; Dual drug release; Individual dosing; Personalized medicine; Solid Dosage Pen