系统生物学和体工程,以克服口服的吸收障碍:剂型优化案例研究,临床翻译之前
Puneet Tyagi1, Chandresh Patel1, Kimberly Gibson2
1Dosage Form Design and Development, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20878, USA.
Pharmaceutics
|October 28, 2023
概括
开发像MEDI7219这样的口服配方与透增强剂 (二氧化和甲酸) 在狗中实现了显著的口服生物可用性,为注射提供了潜在的替代品.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 生物技术是生物技术.
背景情况:
- 口服酸面临着诸如低生物可用性和高可变性等挑战.
- 梅迪7219是一种稳定,脂化葡萄糖类1-激动性.
- 鉴定出基酸盐 (Na CDC) 和基酸盐 (PG) 是有效的透增强剂.
研究的目的:
- 开发和优化MEDI7219的口服药片配方.
- 为了评估不同型号的药片在狗体内体内的性能.
- 为了提高MEDI7219.9的口服生物利用性和减少药物动力学变异性.
主要方法:
- 立即释放片剂的配方包括Na CDC和PG.
- 在pH值≥5.5溶解的肠道涂层的应用,用于上部十二指肠向.
- 开发持续释放配方,使用 Carbopol 和在 pH ≥ 7.0 溶解的肠道涂层.
- 测试一种专有延迟释放侵蚀性屏障层平板电脑 (OralogiKTM).
- 在体内对狗进行的药理动力学研究.
主要成果:
- 优化的药片配方在狗中实现了MEDI7219绝对口服生物利用率高达10.1%.
- 对于MEDI7219,药物动力学变异性降低到26%的最低水平.
- 不同的配方策略显示出不同的释放特征和吸收特征.
结论:
- 成功开发了MEDI7219的口服药片配方,提高了生物可用性和降低了变异性.
- 优化的配方显示出对临床开发的希望,作为注射的替代品.
- 使用先进的涂层技术向胃肠道提供向的输送对于的口服输送至关重要.
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