Observations in simultaneous microencapsulation of 5-fluorouracil and leucovorin for combined pH-dependent release

被引:35
作者
Lamprecht, A [1 ]
Yamamoto, H [1 ]
Takeuchi, H [1 ]
Kawashima, Y [1 ]
机构
[1] Gifu Pharmaceut Univ, Lab Pharmaceut Engn, Gifu 5028585, Japan
基金
日本学术振兴会;
关键词
colon delivery; colorectal cancer; microspheres; 5-fluorouracil; leucovorin;
D O I
10.1016/j.ejpb.2004.09.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 Pm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3 +/- 9.7%; LV, 81.4 +/- 8.6%) compared to P-4135F (5-FU, 48.3 +/- 2.0%; LV, 55.4 +/- 2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h. while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:367 / 371
页数:5
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