title: Preparation and evaluation of a melt pelletised paracetamol/stearic acid sustained release delivery system.
abstract: The potential of a sustained release formulation for paracetamol produced by melt pelletisation was investigated. The chosen formulation was based on the combination of stearic acid as a melting binder and anhydrous lactose as a filler. After determination of the size distribution, the pellet characterisation included scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), specific surface area and true density determination. Hence, the in vitro release from every single size fraction (2000, 1250, 800, 630, <630 microm) was evaluated and the release mechanism was analysed with the help of an appropriate mathematical model. The results of drug content and superficial atomic composition were found to be constant in all pellets size fractions, attesting the ability of melt pelletisation in a high shear mixer to form a product with homogeneous composition. The mathematical model is built on the hypotheses that drug diffusion and solid drug dissolution in the release environment are the key phenomena affecting drug release kinetics. Smaller classes apart (particles are not perfectly spherical), the comparison between model best fitting and experimental data indicated the reasonability of these hypotheses. Moreover, model reliability is proved by its ability of predicting drug release from a known mixture of the above mentioned particles classes.
authors.affiliation: Department of Chemical, Environmental and Raw Materials Engineering, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy. mariog@dicamp.univ.trieste.it
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Dario
authors.initials: D
authors.lastname: Voinovich
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Moneghini
authors.forename: Erica
authors.initials: E
authors.lastname: Franceschinis
authors.forename: Beatrice
authors.initials: B
authors.lastname: Perissutti
authors.forename: Jelena
authors.initials: J
authors.lastname: Filipovic-Grcic
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012995:Solubility; D013229:Stearic Acids / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D004343:Drug Implants; D013229:Stearic Acids; D000082:Acetaminophen; C031183:stearic acid