Development of stable liquid glucagon formulations for use in artificial pancreas.
Development of stable liquid glucagon formulations for use in artificial pancreas.
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DOI：
10.1177/1932296814555541
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发表时间：
2015-01-01
影响因子：
5
通讯作者：
De Souza, Errol
中科院分区：
文献类型：
--
作者：
Pohl, Roderike;Li, Ming;De Souza, Errol
治疗糖尿病的一种有前途的方法是开发全自动人工/仿生胰腺系统，该系统使用胰岛素和胰高血糖素来维持正常血糖。目前尚不存在胰高血糖素的物理和化学稳定的液体制剂。我们的目标是开发一种胰高血糖素制剂，其作为澄清和无凝胶溶液稳定，不含原纤维，并且具有在供应链中储存所需的长期保质期，在37°C下至少7天的短期稳定性，以及用于双激素泵的泵相容性。我们报告了两个不同家族的稳定液体胰高血糖素制剂的开发，其利用表面活性剂或表面活性剂样赋形剂（LMPC和DDM）潜在地通过胶束的形成和胰高血糖素分子之间的相互作用的防止来“溶解”胰高血糖素。所提供的数据证明了在5°C下的长期物理和化学稳定性（约2年）、在加速37°C测试条件下的短期稳定性（长达1个月）、长达9天的泵相容性以及犬和糖尿病猪中的充分葡萄糖反应。这些稳定的胰高血糖素制剂显示出在人工胰腺系统中进一步开发的实用性和前景。
A promising approach to treat diabetes is the development of fully automated artificial/bionic pancreas systems that use both insulin and glucagon to maintain euglycemia. A physically and chemically stable liquid formulation of glucagon does not currently exist. Our goal is to develop a glucagon formulation that is stable as a clear and gel-free solution, free of fibrils and that has the requisite long-term shelf life for storage in the supply chain, short-term stability for at least 7 days at 37°C, and pump compatibility for use in a bihormonal pump. We report the development of two distinct families of stable liquid glucagon formulations which utilize surfactant or surfactant-like excipients (LMPC and DDM) to "immobilize" the glucagon in solution potentially through the formation of micelles and prevention of interaction between glucagon molecules. Data are presented that demonstrate long-term physical and chemical stability (~2 years) at 5°C, short-term stability (up to 1 month) under accelerated 37°C testing conditions, pump compatibility for up to 9 days, and adequate glucose responses in dogs and diabetic swine. These stable glucagon formulations show utility and promise for further development in artificial pancreas systems.