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Improved Dissolution of Dipyridamole with the Combination of pH-Modifier and Solid Dispersion Technology.

Authors
  • Kojo, Yoshiki1
  • Matsunaga, Saori1
  • Suzuki, Hiroki1
  • Taniguchi, Chika2
  • Kawabata, Yohei2
  • Wada, Koichi2
  • Yamauchi, Yukinori3
  • Seto, Yoshiki1
  • Sato, Hideyuki1
  • Onoue, Satomi1
  • 1 Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka.
  • 2 Department of Chemistry, Manufacturing and Control, Kobe Pharma Research Institute, Nippon Boehringer Ingelheim Co., Ltd.
  • 3 Department of Pharmaceutical Physical Chemistry, College of Pharmaceutical Sciences, Matsuyama University.
Type
Published Article
Journal
Chemical and Pharmaceutical Bulletin
Publisher
Pharmaceutical Society of Japan
Publication Date
Jan 01, 2017
Volume
65
Issue
5
Pages
426–431
Identifiers
DOI: 10.1248/cpb.c16-00714
PMID: 28458364
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The aim of this study was to develop a pH-independent release formulation of dipyridamole (DP) by the combined use of pH-modifier technology and solid dispersion (SD) technology employing enteric polymer, Eudragit® S100 (Eud). Tartaric acid (TA) was selected as an appropriate pH-modifier in terms of improving the dissolution behavior of DP under neutral conditions. Upon optimization of the ratio of TA to DP, SD of DP with Eud and TA (SD-Eud/DP/TA) was prepared by a freeze-drying method. Scanning electron microscopic images revealed that DP was dispersed in the polymer in SD-Eud/DP/TA, and DP in SD-Eud/DP/TA was in an amorphous state, supported by powder X-ray diffraction and differential scanning calorimetry analyses. The dissolution behavior of SD-Eud/DP/TA was not dependent on the pH of the medium, although SD-Eud/DP exhibited very limited dissolution behavior under neutral conditions. Spectroscopic analysis suggested that there might be inter-molecular interaction among DP, TA and enteric polymer in SD-Eud/DP/TA, possibly leading to the stable pH-independent dissolution behavior of SD-Eud/DP/TA. TA in SD-Eud/DP/TA promoted the degradation of DP, suggesting that improving the stability of DP in SD-Eud/DP/TA might be key for its practical use. From these results, pH-independent dissolution behavior of SD-Eud/DP/TA could be achieved by an enteric polymer-based solid dispersion with a pH-modifier.

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