博森坦单水化合物和西尔德纳菲尔基作为两种伴侣,使配方成为可能
Dominik Strojewski1, Sebastian Lalik2, Florence Danède3
1Jagiellonian University, Medical College, Faculty of Pharmacy, Department of Pharmaceutical Technology and Biopharmaceutics, PL-30688 Cracow, Poland; Doctoral School of Medical and Health Sciences, Jagiellonian University in Cracow, PL-31530, Poland.
西尔德纳菲尔和博森坦的联合变形改善了肺动脉高血压 (PAH) 治疗的溶解性和生物可用性. 这种方法增强了固定剂量组合疗法的药物配方开发.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 肺动脉高血压 (PAH) 通常用西尔代纳菲尔和博森坦治疗.
- 这两种药物都具有较差的水溶性,使其口服生物利用率限制在50%左右.
- 西尔德纳菲尔是一种弱基,博森坦是一种弱酸,为共同形态配方提供了机会.
研究的目的:
- 为了研究西尔代纳菲尔和博森坦的联合形态化.
- 评估共形态化是否可以提高溶解度并实现超和.
- 探索开发用于治疗PAH的新固定剂量组合药物的潜力.
主要方法:
- 共同形态配方是使用高能球磨粉制备的.
- 固态特性的特征是XRD,DSC,FT-MIR和介电光谱学.
- 分析了粒子大小,表面湿度和微观结构;开发了一种新的HPLC-DAD方法来量化药物.
主要成果:
- 在西尔代纳菲尔基中成功制造了与分子分散博森坦的二进制配方.
- 含量低于50%的西尔代纳菲尔配方表现出最佳的热稳定性.
- 这些配方表现出能够在酸盐缓冲盐水 (PBS) 中形成持久的博森坦超和.
结论:
- 同形化是一种可行的策略,可以提高西尔代纳菲尔和博森坦的溶解性和生物可用性.
- 开发的共同形态系统可以实现和稳定超和.
- 这项研究有助于开发用于肺动脉高血压的新型固定剂量组合疗法.
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