Preparation in high-shear mixer of sustained-release pellets by melt pelletisation

The preparation of sustained-release pellets by melt pelletisation was inve stigated in a 10-1 high shear mixer and ternary mixtures containing stearic acid as a melting binder, anhydrous lactose as a filler and theophylline a s a model drug. A translated Doehlert matrix was applied for the optimisati on of process variables and duality control of pellets characteristics. Aft er determination of size distribution, the pellets were characterised with scanning electron microscopy, X-ray photoelectron spectroscopy and porosime tric analysis. Finally, the in vitro release from every single size fractio n was evaluated and the release mechanism was analysed. Since the drug rele ase rate decreased when enhancing the pellet size fraction, the 2000-mu m f raction, exhibiting a substantially zero-order release, was selected for fu rther in vivo biovailability studies. These data demonstrated that pellets based on the combination of stearic acid and lactose can be used to formula te sustained release pellets for theophylline. (C) 2000 Elsevier Science B. V. All rights reserved.