开发和评估一个模型,描述释放特征的新莱特醇长效注射配方的发展和评估
Adriana Castiñeiras-Pardines1, Gema López-Ginés2, Gastón García-Orueta3
1Department of Pharmaceutical Sciences, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Spain; Laboratorios Farmacéuticos Rovi, S.A., Granada, Spain.
概括
这项研究开发了一种新的长效注射植入物,用于改善乳腺癌治疗的坚持. 研究的特点是影响药物释放的配方因素,有助于强大的产品开发和质量控制.
科学领域:
- 制药和药物输送 制药和药物输送
背景情况:
- 乳腺癌等慢性疾病往往需要长期服用口服药物,导致患者不良的坚持和潜在的疾病进展.
- 长效注射 (LAI) 植入物为口服药物提供了替代品,旨在提高生物可用性,减少血水平的变化,并提高治疗遵守性.
研究的目的:
- 开发和描述一种新型的聚合物,可生物降解,在现场形成长效植入物,用于输送莱特醇.
- 通过评估体外溶解和使用预测建模来了解药物释放动力学来优化配方和开发过程.
主要方法:
- 开发了一套含有莱特醇,聚乳酸和二甲基硫氧化物用于溶解和肌肉内注射的两支注射器套件.
- 利用了实时和加速的体外溶解研究,对15种具有不同关键物质属性 (CMA) 的莱特醇LAI配方进行了实时和加速的体外溶解研究.
- 应用Weibull分布建模来分析释放特征和估计注射期间的剂量损失.
主要成果:
- 第一阶释放速率常数 (KD) 在加速条件下比实时高1.87倍.
- 配方粘度显著影响释放:较高的粘度减少了KD的30%,而较低的粘度增加了1.34倍.
- 确定了关键的配方特征,以定量控制药物释放动力学.
结论:
- 这项研究提供了对莱特醇LAI植入物配方的基本理解,使得能够开发出坚固的产品.
- 这项研究有助于为未来的莱特醇LAI配方制定关键质量控制规范.
- 这些发现为潜在的用临床前和临床数据进行体外-体内相关性研究 (IVIVC) 铺平了道路.
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