酸盐缓冲干扰了普拉佐辛化在综合溶解测试中的溶解.
Hiroshi Sudaki1, Katsuyoshi Fujimoto1, Koichi Wada1
1Nippon Boehringer Ingelheim Co. Ltd., 6-7-5 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
Drug metabolism and pharmacokinetics
|July 2, 2023
概括
普拉佐辛化 (PRZ-HCl) 溶解显示,由于盐的形成,酸盐缓冲区没有超和. 这影响了体内预测,因为肠液使用的是二碳酸盐系统,而不是酸盐.
科学领域:
- 制药科学 制药科学
- 物理化学 物理化学
- 药物运输 药物运输 药物运输
背景情况:
- 超和对于口服药物吸收至关重要.
- 普拉佐辛化 (PRZ-HCl) 呈现出不寻常的溶解行为.
- 了解PRZ-HCl溶解是预测体内性能的关键.
研究的目的:
- 为了研究在普拉佐辛化 (PRZ-HCl) 溶液中缺乏超和.
- 为了确定在PRZ-HCl溶解过程中发生的固态转化.
- 评估酸盐缓冲器适用于模拟体内溶解的适用性.
主要方法:
- 使用摇法确定平衡溶解度.
- 溶解测试是使用综合法进行的.
- 通过拉曼光谱学对残余粒子进行固态分析.
主要成果:
- 在pH 6.5以下的酸盐缓冲器中,PRZ-HCl形成了酸盐,降低了溶解度.
- 在pH 6.5以上,PRZ-HCl转化为其自由基 (PRZ-FB),匹配非缓冲溶解度.
- 在溶解试验中,PRZ-HCl迅速转化为酸盐,然后慢慢转化为PRZ-FB.
结论:
- 酸盐缓冲器由于不同的缓冲系统 (二碳酸盐与酸盐) 不能准确地反映体内溶解.
- PRZ酸盐的形成抑制了超和,影响了溶解概况.
- 药物配方和溶解测试需要考虑生理缓冲系统,以准确地进行体内预测.
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