title: Cold extrusion as a continuous single-step granulation and tabletting process.
abstract: The potential of cold extrusion as a continuous granulation/tabletting technique was investigated. Extrudates (X, 9 mm) were produced using twin-screw extrusion, cut manually into tablets (thickness, 4 mm) and dried at 25 degrees C for 20 h. alpha-Lactose monohydrate (200 M) was used as an excipient, PVP (Kollidon K30) and water as binders, and hydrochlorothiazide as the model drug. The influence of formulation (water content, PVP addition, drug incorporation) and process (total input rate and screw speed) parameters on the process (torque, die pressure, visual evaluation of tablets) and on the tablet properties (tensile strength, friability, disintegration time, porosity) was evaluated. Formulation, as well as process parameters, affected the process feasibility, but had only a minor effect on the tablet properties at conditions that allowed continuous tablet production. All alpha-lactose monohydrate tablets formulated without and with PVP and produced at optimum conditions showed tensile strengths above 0.7 and 1.5 MPa, friabilities below 1.0 and 0.9%, and disintegration times below 1 and 8 min, respectively. This technique allows single-step granulation/tabletting of pure alpha-lactose monohydrate, indicating that cold extrusion could be used as alternative tablet production technique for ingredients with poor compaction properties. As the tablets prepared by extrusion have a much higher porosity compared with conventional tablets, this technique could also be useful for tablet production of formulations with poor disintegrating properties.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: E I
authors.initials: EI
authors.lastname: Keleb
authors.forename: A
authors.initials: A
authors.lastname: Vermeire
authors.forename: C
authors.initials: C
authors.lastname: Vervaet
authors.forename: J P
authors.initials: JP
authors.lastname: Remon
mesh_terms: D002626:Chemistry, Pharmaceutical; D003080:Cold Temperature; D007785:Lactose / Q000138:chemical synthesis; D011145:Polyvinyls / Q000138:chemical synthesis; D013607:Tablets / Q000138:chemical synthesis*; D013678:Technology, Pharmaceutical / Q000379:methods*; D017155:Wettability
chemical_list: D011145:Polyvinyls; D013607:Tablets; D007785:Lactose