The purpose of this study was to evaluate and compare the ability of the macromolecular conjugates and microspheres to modify the
release rate of gemfibrozil (Gem). Gem was covalently linked to two similar polymers: poly[a,b-(N-2-hydroxyethyl-DL-aspartamide)]
(PHEA) and poly[a,b-(N-3-hydroxypropyl-DL-aspartamide)] (PHPA) by an ester linkage. The polymer–drug conjugates obtained
(PHEA–G(1–3) and PHPA–G) differ in weight-average molecular weight, length of spacer and Gem content. Microspheres, composed of
chitosans of different molecular weight alone or as a mixture with (2-hydroxypropyl)methylcellulose (HPMC), PHEA or PHPA and with
different theoretical polymer/drug ratio (2:1 and 3:1, w/w) were prepared by spray drying. The microparticulate systems were
morphologically characterised by scanning electron microscopy, particle size analysis and Gem content was determined. In vitro
dissolution tests were performed to evaluate the feasibility of conjugates and microspheres in modulating Gem release. The results
obtained show that microspheres are always suitable to modulate Gem release and that the best conditions are achieved by microspheres
composed of the low molecular weight chitosan (CL) combined with PHPA or HPMC with either 2:1 or 3:1 (w/w) polymer/drug ratio.
The PHEA–G conjugates exhibited rapid Gem release within less than 2 h, while the PHPA–G conjugate showed sustained Gem release
profiles over a 10-h period.
2002 Elsevier Science B.V. All rights reserved.
