使用理性设计优化儿科配方:探索无形固体分散技术与特尔比纳芬化作为案例研究
Izabelle Amorim Ferreira Boza1, Stéfani Laise da Silva1, Nicolly Bittencourt Guedes2
1Department of Chemistry, Center for Physical and Mathematical Sciences, Federal University of Santa Catarina, Florianópolis, SC, 88040-900, Brazil.
AAPS PharmSciTech
|January 17, 2025
概括
由于其溶解度较低,为特比纳芬化物 (TER) 开发儿科抗真菌配方具有挑战性. 研究人员确定Soluplus®是无形固体分散的有希望的载体,增强了儿童的TER溶解性和生物可用性.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 儿科配方 儿科配方 儿科配方
背景情况:
- 儿科配方面临着独特的挑战,特别是对于像特比纳芬化 (TER) 这样的药物,这是一种具有较低水溶性的抗真菌剂.
- 头炎是一种常见的儿科真菌感染,需要有效的口服治疗,但TER的溶解性差阻碍了口服生物可用性.
研究的目的:
- 合理选择合适的,经过儿科批准的载体,以提高TER的表面溶解度.
- 使用喷雾干燥开发TER的无形固体分散 (ASD),以改善儿科患者的口服生物可用性.
主要方法:
- 评估溶解度参数,平衡溶解度,以及用于载体选择的儿科剂量数.
- 使用了Plasdone S-360 ULTRA®,HPMCAS L和Soluplus®作为潜在的载体.
- 使用各种技术,描述药物载体相互作用和固态特性.
- 用选择的载体进行喷雾干燥的TER的准备ASD.
主要成果:
- TER的溶解度依赖于pH值,在pH值6.5的缓冲剂中观察到的最高溶解度为10%的Soluplus®.
- 在6岁以上的儿童中,Soluplus®产生的儿科用剂量数最少 (0.23).
- 喷雾干燥的ASD显著提高了TER的表面溶解度,并保持了长时间的超和.
- 没有观察到相变或显著的药物载体相互作用.
结论:
- 索鲁普卢斯 (Soluplus®) 是一种适合用于开发儿科口服配方TER无形固体分散物的载体.
- 使用Soluplus®的TER喷雾干燥ASD为改善儿童口服生物可用性和疗效提供了一个有希望的策略.
- 这种方法解决了为儿科患者开发有效的口服抗真菌治疗的挑战.
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