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
Me. Aulton et al., 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, Drug development and industrial pharmacy, 20(20), 1994, pp. 3069-3104
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.