Lung Drug Delivery with Carbon Dioxide Aerosol Inhalers

使用二氧化碳气溶胶吸入器进行肺部药物输送

• 批准号: 6626080
• 负责人: Brian N Hansen
• 金额: $ 36.65万
• 依托单位: AEROPHASE, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-09 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626080
• 关键词: aerosols; carbon dioxide; dosage; dosage forms; drug delivery systems; drug design /synthesis /production; inhalation drug administration; technology /technique development

DESCRIPTION (Applicant's abstract): Asthma is one of the most common and costly illnesses in the United States, and drug formulation delivered via metered inhalers (MDIs) represent the primary treatment method for asthma sufferers. A key current issue in this arena is that the chlorofluorocarbon (CFC) propellants traditionally used in MDIs are being phased out by the government due to their high ozone-depletion potential--thus presenting a need for a replacement that is safe, effective, and economical. Although hydrofluoroalkane (HFA) propellants were thought to be a good candidate, potential problems include toxicity, incompatibility with devices, incompatibility with FDA-approved inhaler surfactants, and reduced bioavailability of some drugs. During Phase I Aerophase clearly demonstrated the feasibility of using CO2 as the next-generation propellant for pulmonary aerosol delivery of pharmaceuticals. Advantages include zero ozone-depletion potential, low toxicity, and the ability to administer to the lungs lipophilic drugs that cannot currently be delivered by any other method. A novel, high performance MicroBurst MDI design was tested successfully. The Phase II project proposed here would allow Aerophase to optimize candidate CO2-based formulations (e.g. albuterol, beclomethasone dipropionate, and budesonide) and to complete the design, development, and validation of the one or more MDIs in preparation for FDA approval and ultimate commercialization. PROPOSED COMMERCIAL APPLICATION: Beyond the initial goal of producing CO2-based drug formulations and MDIs for the effective treatment of asthma, the system we are pursuing could also be used effectively to deliver antibiotics to reduce death from pneumonia, possibly replace the need to inject insulin, deliver drugs that cannot be administered by any other method, provide targeted lung cancer therapy, and deliver rapid intervention against chemical warfare agents.

描述（申请人摘要）：哮喘是一种最常见和昂贵的 疾病在美国，和药物制剂提供通过计量 吸入器（MDI）代表哮喘患者的主要治疗方法。一 当前在这个竞技场中的关键问题是， 传统上用于计量吸入器的推进剂正在被政府逐步淘汰 由于其高臭氧消耗潜能，因此需要 安全、有效和经济的更换。虽然氢氟烷烃 (HFA)推进剂被认为是一个很好的候选者，潜在的问题 包括毒性、与装置不相容性、与 FDA批准的吸入器表面活性剂，并降低了一些药物的生物利用度。 在第一阶段，Aerophase清楚地证明了使用CO2作为 用于肺部气雾剂递送的下一代推进剂 大药厂优点包括零臭氧消耗潜能，低 毒性，以及向肺部施用亲脂性药物的能力， 目前无法通过任何其他方法交付。一种新颖的高性能 成功测试了MicroBurst MDI设计。第二阶段项目建议 这将允许Aerophase优化候选CO2基制剂（例如， 沙丁胺醇、二丙酸倍氯米松和布地奈德），并完成 设计、开发和验证一种或多种计量吸入器， FDA批准和最终商业化。 拟定商业应用：除了生产用于有效治疗哮喘的二氧化碳药物制剂和计量吸入器的最初目标之外，我们正在追求的系统还可以有效地用于提供抗生素以减少肺炎死亡，可能取代注射胰岛素的需要，提供无法通过任何其他方法给药的药物，提供有针对性的肺癌治疗，并提供针对化学战剂的快速干预。