THE STRENGTH AND COMPACTION OF MILLISPHERES - THE DESIGN OF A CONTROLLED-RELEASE DRUG-DELIVERY SYSTEM FOR IBUPROFEN IN THE FORM OF A TABLETCOMPRISING COMPACTED POLYMER-COATED MILLISPHERES

This paper reviews a case study of the design of a controlled-release drug delivery system for ibuprofen in the form of a tablet comprising compacted polymer-coated millispheres (multiparticulate pellets). The particular challenge was to prepare coated millispheres of ibuprofen ( a high-dose drug) with the addition of minimal excipients so that the drug-release retarding polymeric membrane surrounding the millispheres remains intact during and after tablet compression, disintegration an d release of the millispheres. The study included (a) the design of th e uncoated core and its manufacture by wet massing, extrusion, spheron ization and drying; (b) the coating of these millispheres with a range of possibly suitable polymers; (c) an assessment of the drug release profiles from these pellets; (d) the quantification by indentation rhe ology of the mechanical properties of the polymer films used to coat t he spheres; (e) the measurement of the mechanical properties of indivi dual uncoated and coated millispheres and f. the design, manufacture a nd evaluation of compressed tablets containing coated millispheres. Th e matching of millisphere and polymer mechanical properties was found to be essential in order to ensure minimal damage to the millispheres and the release of virtually intact coated spheres without destruction of their retarded drug-release characteristics. Aqueous polymeric dis persions which formed a film with similar elastic and tensile properti es to the uncoated millisphere formulation resulted in the most satisf actory film coating for application to spherical particles which must withstand compaction. Those polymeric films exhibiting significantly g reater resilience than the uncoated cores were inappropriate for the f ilm coating of millispheres for compaction into tablets.