Plastic Parenteral Containers With Superior Oxygen Barrier Properties

项目摘要 与第一型硼硅酸盐玻璃相比，塑料作为肠外营养材料具有几个关键优势 药物容器(例如小瓶和预注满的注射器)。塑料不容易破损，而且可以 模制成比玻璃更复杂的形状，尺寸公差更紧。此外，塑料不是 易受玻璃分层的影响-这是该行业的一个主要问题，药物产品在化学上攻击其 玻璃容器，导致玻璃碎片脱落进入药物。 塑料容器的主要缺点是它们的透氧性相对较高，这可能 缩短氧气敏感药物的保质期。通过将阻隔涂层涂覆到塑料容器上 大大降低了其透氧性，这一缺点是可以消除的。可行的候选材料 由此使该阻挡涂层具有与玻璃相似的化学成分，从而具有类似的敏感性 对化学物质的攻击。因此，阻隔涂层需要额外钝化层的保护。 在第一阶段，摩擦膜研究公司优化了摩擦屏蔽™，这是一种双层涂层系统，由 高效的氧气阻隔层和保护性钝化层，用于塑料非肠道容器。 摩擦屏蔽™涂层塑料瓶被证明具有与玻璃瓶相似的氧气阻隔性能。 此外，钝化层被显示为有效地保护氧阻挡层不受普通 注射用制剂中使用的缓冲液。此外，试验还表明，对于摩擦屏蔽™涂层塑料， 环氧乙烷灭菌瓶对其阻氧性能无影响。 第二阶段将以第一阶段的发现为基础，证明摩擦盾™的商业可行性 从制造的角度来看，技术。摩擦屏蔽™涂层参数将使用 可扩展的处理设备，可实现极低的透氧率，几乎不会对 由普通药物配方引起的化学攻击。将开发一种高速检测技术来验证 每个容器上都有(肉眼看不见的)氧气屏障涂层，以保证质量 目的。此外，将进行一项全面的研究，以验证 肾上腺素储存在摩擦盾牌™涂覆的塑料瓶中。该项目将以创建一个 中试规模的涂层系统，将演示沉积摩擦盾™涂层所需的所有步骤 系统可以集成到一个连续的制造过程中。飞行员的机器将显示出- 如何在生产的同时将大规模生产转移给潜在的被许可方 摩擦防护™涂层容器，可提供给客户进行评估。 设备制造商和制药商长期以来一直希望有一种适合氧气使用的容器- 敏感药物，不会有任何破损或玻璃分层的担忧。如果成功，TriboShield™ 将提供这一点，使制药业能够过渡到更理想的塑料容器。

PROJECT ABSTRACT Plastic offers several key advantages over Type 1 borosilicate glass as a material for parenteral pharmaceutical containers (e.g. vials and prefilled syringes). Plastic is not prone to breakage, and can be molded into more complex shapes with tighter dimensional tolerances than glass. Additionally, plastic is not susceptible to glass delamination — a major problem in the industry where a drug product chemically attacks its glass container, resulting in glass fragments flaking off into the drug. The primary disadvantage of plastic containers is their relatively high oxygen permeability, which can reduce the shelf life of oxygen-sensitive drugs. By applying a barrier coating to a plastic container that drastically lowers its oxygen permeability, this shortcoming can be eliminated. The viable candidate materials from which to make this barrier coating have similar chemistries to glass, and thus have similar susceptibility to chemical attack. Therefore, the barrier coating requires the protection of an additional passivating layer. In Phase I, TriboFilm Research optimized TriboShield™, a bi-layer coating system consisting of a highly effective oxygen barrier layer plus a protective passivation layer for plastic parenteral containers. TriboShield™ coated plastic vials were shown to have oxygen barrier properties similar to those of glass vials. Further, the passivation layer was shown to be effective in protecting the oxygen barrier layer from common buffers used in parenteral formulations. In addition, it was shown that subjecting TriboShield™ coated plastic vials to ethylene oxide sterilization had no effect on their oxygen barrier performance. Phase II will build on the Phase I findings to prove the commercial viability of the TriboShield™ technology from a manufacturing standpoint. The TriboShield™ coating parameters will be optimized using scalable processing equipment to achieve extremely low oxygen permeability and little to no susceptibility to chemical attack by common drug formulations. A high-speed inspection technique will be developed to verify the presence of the (invisible to the eye) oxygen barrier coating on each container for quality assurance purposes. In addition, a comprehensive study will be performed to verify the long-term stability of epinephrine stored in TriboShield™ coated plastic vials. This project will culminate with the creation of a pilot-scale coating system that will demonstrate how all the steps required to deposit the TriboShield™ coating system can be integrated into a continuous manufacturing process. The pilot machine will show the know- how for full-scale manufacturing that can be transferred to potential licensees, while also producing TriboShield™ coated containers that can be provided to customers for evaluation. Device manufacturers and drug makers have long desired a container suitable for use with oxygen- sensitive drugs that is free of any concerns with breakage or glass delamination. If successful, TriboShield™ will provide this, enabling the pharmaceutical industry to transition to more desirable plastic containers.