Plastic Parenteral Containers With Superior Oxygen Barrier Properties

具有卓越氧气阻隔性能的塑料注射容器

• 批准号: 9765366
• 负责人: Daniel Everett Jonsen
• 金额: $ 91.38万
• 依托单位: TRIBOFILM RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765366
• 关键词: Buffers; Catecholamines; Chemical Warfare; Chemistry; Complex; Data; Deposition; Devices; Dimensions; Disadvantaged; Drug Formulations; Drug Industry; Drug-sensitive; Effectiveness; Emergency Situation; Epinephrine; Equipment; Ethylene Oxide; Evaluation; Eye; Film; Formulation; Glass; Industry; Intellectual Property; Licensing; Life; Manuals; Manufacturer Name; Measurement; Measures; Medical; Methods; Molds; Optics; Outcome; Oxygen; Performance; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Plastics; Polymers; Predisposition; Process; Production; Property; Research; Risk; Sampling; Shapes; Speed; Sterilization; Surface; Syringes; System; Techniques; Technology; Thick; Vial device; manufacturing process; oxidation; phase 2 study; process optimization; prospective; quality assurance; scale up

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.

项目摘要 与1型硼硅酸盐玻璃相比，塑料作为胃肠外给药材料具有几个关键优势 药物容器（例如小瓶和预充式注射器）。塑料不易破碎， 模塑成比玻璃更复杂的形状，具有更严格的尺寸公差。此外，塑料不 易受玻璃脱层的影响-这是药物产品化学侵蚀其 玻璃容器，导致玻璃碎片剥落到药物中。 塑料容器的主要缺点是它们相对高的透氧性，这可能 减少氧敏感药物的保质期。通过将阻隔涂层施加到塑料容器上， 大大降低了其透氧性，可以消除这一缺点。可行的候选材料 从而使该阻隔涂层具有与玻璃相似的化学性质， 化学攻击。因此，屏障涂层需要额外的钝化层的保护。 在第一阶段，TriboFilm Research优化了TriboShield™，这是一种双层涂层系统， 高效的氧气阻隔层加上保护性钝化层，用于塑料注射容器。 TriboShield™涂覆的塑料小瓶显示出具有与玻璃小瓶类似的氧气阻隔性能。 此外，钝化层被示出为有效地保护氧阻挡层免受常见的腐蚀。 肠胃外制剂中使用的缓冲液。此外，研究表明，TriboShield™涂层塑料 小瓶经环氧乙烷灭菌对其氧气阻隔性能没有影响。 第二阶段将在第一阶段研究结果的基础上，证明TriboShield™的商业可行性。 从制造业的角度来看。TriboShield™涂层参数将通过以下方式进行优化： 可扩展的处理设备，以实现极低的氧气渗透性和几乎不敏感性， 普通药物制剂的化学攻击。将开发一种高速检查技术， 每个容器上都有（肉眼不可见的）氧气阻隔涂层，以保证质量 目的此外，还将进行一项综合研究，以验证 储存在TriboShield™涂层塑料小瓶中的肾上腺素。该项目将以创建一个 中试规模的涂层系统，将演示存款TriboShield™涂层所需的所有步骤 系统可以集成到一个连续的生产过程中。试验机器会显示已知的- 如何进行全面的制造，可以转移到潜在的许可证，同时也生产 TriboShield™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与氧气一起使用的容器， 敏感性药物，没有任何破损或玻璃分层的问题。如果成功，TriboShield™ 将提供这一点，使制药行业过渡到更理想的塑料容器。