title: Continuous twin screw melt granulation of glyceryl behenate: Development of controlled release tramadol hydrochloride tablets for improved safety.
abstract: Interest in granulation processes using twin screw extrusion machines is rapidly growing. The primary objectives of this study were to develop a continuous granulation process for direct production of granules using this technique with glyceryl behenate as a binder, evaluate the properties of the resulting granules and develop controlled release tablets containing tramadol HCl. In addition, the granulation mechanism was probed and the polymorphic form of the lipid and drug release rate were evaluated on stability. Granules were prepared using a Leistritz NANO16 twin screw extruder operated without a constricting die. The solid state of the granules were characterized by differential scanning calorimetry and X-ray diffraction. Formulated tablets were studied in 0.1N HCl containing 0-40% ethanol to investigate propensity for alcohol induced dose dumping. The extrusion barrel temperature profile and feed rate were determined to be the primary factors influencing the particle size distribution. Granules were formed by a combination immersion/distribution mechanism, did not require subsequent milling, and were observed to contain desirable polymorphic forms of glyceryl behenate. Drug release from tablets was complete and controlled over 16 h and the tablets were determined to be resistant to alcohol induced dose dumping. The drug release rate from the tablets was found to be stable at 40°C and 75% relative humidity for the duration of a 3 month study.
authors.affiliation: The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA; DisperSol Technologies, 111 W. Cooperative Way, Suite 200, Georgetown, TX 78626, USA. Electronic address: jmkeen@utexas.edu.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Keen
authors.affiliation: The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
authors.forename: Connor J
authors.initials: CJ
authors.lastname: Foley
authors.affiliation: The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
authors.forename: Justin R
authors.initials: JR
authors.lastname: Hughey
authors.affiliation: The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Bennett
authors.affiliation: GATTEFOSSE SAS, 36, Chemin de GENGAS, Sain-Priest 69804, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jannin
authors.affiliation: GATTEFOSSE SAS, 36, Chemin de GENGAS, Sain-Priest 69804, France.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Rosiaux
authors.affiliation: GATTEFOSSE SAS, 36, Chemin de GENGAS, Sain-Priest 69804, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Marchaud
authors.affiliation: The University of Texas at Austin, 1 University Station, Austin, TX 78712, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: McGinity
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D005227:Fatty Acids / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011208:Powders; D012995:Solubility; D013607:Tablets; D014147:Tramadol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D005079:Excipients; D005227:Fatty Acids; D011208:Powders; D013607:Tablets; C086409:glyceryl behenate; D014147:Tramadol
keywords: Controlled release; Dose dumping; Melt granulation; Twin screw granulation