Anran Hu1, Chen Chen2, Michael D Mantle3, Bettina Wolf4, Lynn F Gladden2, Ali Rajabi-Siahboomi5, Shahrzad Missaghi5, Laura Mason1, Colin D Melia1. 1. Formulation Insights, School of Pharmacy, Nottingham, NG7 2RD, UK. 2. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 3RA, UK. 3. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, CB2 3RA, UK. mdm20@cam.ac.uk. 4. Food Sciences, School of Biosciences, University of Nottingham, Loughborough, LE12 5RD, UK. 5. Colorcon Inc., Global Headquarters, 275 Ruth Road, Harleysville, Pennsylvania, 19438, USA.
Abstract
PURPOSE: Investigate the extended release behaviour of compacts containing mixtures of hydrophilic HPMC and PEO in hydrating media of differing ionic strengths. METHODS: The extended release behaviour of various HPMC:PEO compacts was investigated using dissolution testing, confocal microscopy and magnetic resonance imaging, with respect to polymer ratio and ionic strength of the hydrating media. RESULTS: Increasing HPMC content gave longer extended release times, but a greater sensitivity to high ionic dissolution environments. Increasing PEO content reduced this sensitivity. The addition of PEO to a predominantly HPMC matrix reduced release rate sensitivity to high ionic environments. Confocal microscopy of early gel layer development showed the two polymers appeared to contribute independently to gel layer structure whilst together forming a coherent and effective diffusion barrier. There was some evidence that poorly swollen HPMC particles added a tortuosity barrier to the gel layer in high ionic strength environments, resulting in prolonged extended release. MRI provides unique, non-invasive spatially resolved information from within the HPMC:PEO compacts that furthers our understanding of USP 1 and USP 4 dissolution data. CONCLUSIONS: Confocal microscopy and MRI data show that combinations of HPMC and PEO have advantageous extended release properties, in comparison with matrices containing a single polymer.
PURPOSE: Investigate the extended release behaviour of compacts containing mixtures of hydrophilic HPMC and PEO in hydrating media of differing ionic strengths. METHODS: The extended release behaviour of various HPMC:PEO compacts was investigated using dissolution testing, confocal microscopy and magnetic resonance imaging, with respect to polymer ratio and ionic strength of the hydrating media. RESULTS: Increasing HPMC content gave longer extended release times, but a greater sensitivity to high ionic dissolution environments. Increasing PEO content reduced this sensitivity. The addition of PEO to a predominantly HPMC matrix reduced release rate sensitivity to high ionic environments. Confocal microscopy of early gel layer development showed the two polymers appeared to contribute independently to gel layer structure whilst together forming a coherent and effective diffusion barrier. There was some evidence that poorly swollen HPMC particles added a tortuosity barrier to the gel layer in high ionic strength environments, resulting in prolonged extended release. MRI provides unique, non-invasive spatially resolved information from within the HPMC:PEO compacts that furthers our understanding of USP 1 and USP 4 dissolution data. CONCLUSIONS: Confocal microscopy and MRI data show that combinations of HPMC and PEO have advantageous extended release properties, in comparison with matrices containing a single polymer.
Authors: Jari T T Leskinen; Mikko A Hakulinen; Marko Kuosmanen; Jarkko Ketolainen; Susanna Abrahmsén-Alami; Reijo Lappalainen Journal: Int J Pharm Date: 2010-11-19 Impact factor: 5.875