Development of a highly stable, nonaqueous glucagon formulation for delivery via infusion pump systems.
Development of a highly stable, nonaqueous glucagon formulation for delivery via infusion pump systems.
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DOI：
10.1177/1932296814565131
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发表时间：
2015-01-01
影响因子：
5
通讯作者：
Prestrelski, Steven J
中科院分区：
文献类型：
--
作者：
Newswanger, Brett;Ammons, Steve;Prestrelski, Steven J
尽管进行了积极的研究工作，但迄今为止，在水性制剂中实现胰高血糖素稳定性（无需重构）的系统的开发未能产生任何临床候选药物。我们开发了一种基于生物相容性药物溶剂二甲亚砜的新型非水胰高血糖素制剂，该制剂在相对高浓度和高温下表现出优异的物理和化学稳定性。本文报道了一种新型、生物相容性、非水性天然人胰高血糖素制剂的开发，该制剂可用于皮下输液泵系统。所提供的数据证明了在假定储存条件下（室温下 >2 年）的物理和化学稳定性以及 Insulet OmniPod() 输液泵的“使用中”稳定性和兼容性。还提供了兔模型皮肤刺激研究的结果以及糖尿病猪模型中胰高血糖素泵给药后的药代动力学/药效学数据。这种非水胰高血糖素制剂适合泵系统的进一步临床开发。
Despite a vigorous research effort, to date, the development of systems that achieve glucagon stability in aqueous formulations (without reconstitution) has failed to produce any clinical candidates. We have developed a novel, nonaqueous glucagon formulation based on a biocompatible pharmaceutical solvent, dimethyl sulfoxide, which demonstrates excellent physical and chemical stability at relatively high concentrations and at high temperatures. This article reports the development of a novel, biocompatible, nonaqueous native human glucagon formulation for potential use in subcutaneous infusion pump systems. Data are presented that demonstrate physical and chemical stability under presumed storage conditions (>2 years at room temperature) as well as "in use" stability and compatibility in an Insulet's OmniPod() infusion pump. Also presented are results of a skin irritation study in a rabbit model and pharmacokinetics/pharmacodynamics data following pump administration of glucagon in a diabetic swine model. This nonaqueous glucagon formulation is suitable for further clinical development in pump systems.