title: Development of starch-based pellets via extrusion/spheronisation.
abstract: A modified starch (high-amylose, crystalline and resistant starch) was evaluated as an alternative excipient to microcrystalline cellulose for pellets prepared via extrusion/spheronisation. Theophylline anhydrous (25%, w/w) was used as a model drug. A binder was necessary to obtain an acceptable yield and the addition of sorbitol improved the surface properties of the pellets. A surface response design with three formulation variables (binder, sorbitol and water level) and one process variable (spheronisation speed) was used to optimise the process and to evaluate pellet yield, sphericity (aspect ratio and two-dimensional shape factor, e(R)), size (mean Feret diameter), friability and disintegration properties. Mixer torque rheometry and solid-state NMR revealed a significant influence of sorbitol on wet mass consistency and pellet properties. A high pellet yield (>90%), acceptable sphericity (AR<1.2), low friability (<0.01%), fast disintegration (<10 min) and complete drug release in less than 20 min for all formulations, demonstrated the potential of this modified starch in formulations intended for extrusion/spheronisation.
authors.affiliation: Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dukić
authors.forename: Raoul
authors.initials: R
authors.lastname: Mens
authors.forename: Peter
authors.initials: P
authors.lastname: Adriaensens
authors.forename: Paul
authors.initials: P
authors.lastname: Foreman
authors.forename: Jan
authors.initials: J
authors.lastname: Gelan
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Chris
authors.initials: C
authors.lastname: Vervaet
mesh_terms: D000465:Algorithms; D000687:Amylopectin / Q000737:chemistry* / Q000592:standards; D000688:Amylose / Q000737:chemistry* / Q000592:standards; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000295:instrumentation / Q000379:methods*; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D021621:Imaging, Three-Dimensional; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D010968:Plasticizers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013012:Sorbitol / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000737:chemistry; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D005079:Excipients; D010968:Plasticizers; D013012:Sorbitol; D002482:Cellulose; D000688:Amylose; D000687:Amylopectin; C008079:hydroxypropylcellulose; D013806:Theophylline; D011205:Povidone