Preparation and in vitro/in vivo characterisation of a melt pelletised paracetamol/stearic acid sustained release delivery system

Issue title: Second International Conference on Biomedical Spectroscopy: From the Bench to the Clinic, London, UK, 5–8 July, 2003

Article type: Research Article

Authors: Grassi, Mario^; | Voinovich, Dario | Grabnar, Iztok | Franceschinis, Erica | Perissutti, Beatrice | Filipovic‐Grcic, Jelena

Affiliations: Department of Chemical, Environmental and Raw Materials Engineering, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy | Department of Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127 Trieste, Italy | Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000 Ljubljana, Slovenia | Department of Pharmaceutics, Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića, 10000 Zagreb, Croatia

Note: [] Corresponding author. Tel.: +39 040 5583435; Fax: +39 040 569823; E‐mail: [email protected].

Abstract: The potential of a sustained release formulation for paracetamol produced by melt pelletisation was investigated. After the production of the pellets, based on the combination of stearic acid as a melting binder and anhydrous lactose as a filler, the 3000–2000 μm size fraction was selected in the light of the promising in vitro dissolution results for further characterisations, including scanning electron microscopy (SEM), X‐ray photoelectron spectroscopy (XPS), specific surface area and true density determination. Hence the release mechanism was analysed with the help of an appropriate mathematical model. The mathematical model was built on the hypotheses that drug diffusion and solid drug dissolution in the release environment are the key phenomena affecting drug release kinetics. Bioavailability of the developed formulation was evaluated in an in vivo study in eight subjects.

Keywords: Melt pelletisation, high shear mixer, paracetamol, sustained release, in vitro dissolution, modelling of drug‐release mechanism, in vivo bioavailability studies

Journal: Spectroscopy, vol. 18, no. 2, pp. 375-386, 2004