Gemfibrozil encapsulation and release from microspheres and macromolecular conjugates

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 [alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly [alpha,beta-(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 It, while the PHPA-G conjugate showed sustained Gem release profiles over a 10-h period. (C) 2002 Elsevier Science B.V. All rights reserved.