Amos Olusegun Abioye1, Rachel Armitage2, Adeola Tawakalitu Kola-Mustapha2,3. 1. Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK. aabioye@dmu.ac.uk. 2. Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, LE1 9BH, UK. 3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, University of Ilorin, Ilorin, Nigeria.
Abstract
PURPOSE: The direct impact of intermolecular attraction between ibuprofen and chitosan on crystal behaviour, saturated solubility and dissolution efficiency of ibuprofen was investigated in order to expand the drug delivery strategy for ibuprofen. METHODS: Amorphous nanoparticle complex (nanoplex) was prepared by controlled drug-polymer nanoassembly. Intermolecular attraction was confirmed with surface tension, conductivity measurements and FTIR spectroscopy. The nanoplex was characterized using DSC, TGA and SEM. The in vitro release kinetics and mechanism of drug release were evaluated using mathematical models. RESULTS: The cmc of ibuprofen decreased significantly in the nanoplex (1.85 mM) compared with pure ibuprofen (177.62 mM) suggesting a remarkable affinity between the chitosan and ibuprofen. The disappearance of ibuprofen melting peak in the nanoplex and the broadened DSC endothermic peaks of the nanoplex indicate formation of eutectic amorphous product which corresponded to higher saturated solubility and dissolution velocity. Ibuprofen (aspect ratio 5.16 ± 1.15) was converted into spherical nanoparticle complex with particle size of 14.96 ± 1.162-143.17 ± 17.5247 nm (36-345 folds reduction) dictated by chitosan concentration. Pure ibuprofen exhibited burst release while the nanoplexes showed both fast and extended release profiles. DE increased to a maximum (81.76 ± 2.1031%) with chitosan concentrations at 3.28 × 10-3 g/dm3, beyond which retardation occurred steadily. Major mechanism of drug release from the nanoplex was by diffusion however anomalous transport and super case II transport did occur. CONCLUSION: Ibuprofen-chitosan nanoplex exhibited combined fast and extended release profile dictated by chitosan concentration. This study demonstrated the potential application of drug-polymer nanoconjugate design in multifunctional regulated drug delivery.
PURPOSE: The direct impact of intermolecular attraction between ibuprofen and chitosan on crystal behaviour, saturated solubility and dissolution efficiency of ibuprofen was investigated in order to expand the drug delivery strategy for ibuprofen. METHODS: Amorphous nanoparticle complex (nanoplex) was prepared by controlled drug-polymer nanoassembly. Intermolecular attraction was confirmed with surface tension, conductivity measurements and FTIR spectroscopy. The nanoplex was characterized using DSC, TGA and SEM. The in vitro release kinetics and mechanism of drug release were evaluated using mathematical models. RESULTS: The cmc of ibuprofen decreased significantly in the nanoplex (1.85 mM) compared with pure ibuprofen (177.62 mM) suggesting a remarkable affinity between the chitosan and ibuprofen. The disappearance of ibuprofen melting peak in the nanoplex and the broadened DSC endothermic peaks of the nanoplex indicate formation of eutectic amorphous product which corresponded to higher saturated solubility and dissolution velocity. Ibuprofen (aspect ratio 5.16 ± 1.15) was converted into spherical nanoparticle complex with particle size of 14.96 ± 1.162-143.17 ± 17.5247 nm (36-345 folds reduction) dictated by chitosan concentration. Pure ibuprofen exhibited burst release while the nanoplexes showed both fast and extended release profiles. DE increased to a maximum (81.76 ± 2.1031%) with chitosan concentrations at 3.28 × 10-3 g/dm3, beyond which retardation occurred steadily. Major mechanism of drug release from the nanoplex was by diffusion however anomalous transport and super case II transport did occur. CONCLUSION:Ibuprofen-chitosan nanoplex exhibited combined fast and extended release profile dictated by chitosan concentration. This study demonstrated the potential application of drug-polymer nanoconjugate design in multifunctional regulated drug delivery.
Entities:
Keywords:
Ibuprofen-chitosan nanoplex; Mechanism of drug release; Solubility parameters; Surface excess; Thermodynamic properties