SUPRAER, High Dose Rate Aerosol Drug Delivery

SUPRAER，高剂量率气雾剂药物输送

• 批准号: 7270090
• 负责人: Donovan B Yeates
• 金额: $ 39.02万
• 依托单位: BIOTECHPLEX CORPORATION
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7270090
• 关键词: Address; Aerosols; Antibiotics; Antineoplastic Agents; Automobile Driving; Breathing; Caliber; Characteristics; Development; Devices; Dose; Dose-Rate; Drug Delivery Systems; Excipients; Generations; Hour; Housing; Inhalation Therapy; Inhalators; Insulin; Irritants; Lead; Liquid substance; Lung diseases; Mannitol; Marketing; Microfluidics; Modeling; Molecular; Nebulizer; Osmolar Concentration; Output; Patients; Pattern; Peptides; Performance; Pharmaceutical Preparations; Phase; Powder dose form; Range; Rate; Regulation; Respiratory System; Risk; Solutions; Solvents; Surface; Suspension substance; Suspensions; System; Technology; Testing; Therapeutic Agents; Time; Tobramycin; United States Food and Drug Administration; aqueous; base; day; design; evaporation; milligram; novel; particle; prototype; respiratory; shear stress; size; small molecule; surfactant

DESCRIPTION (provided by applicant): It has been estimated that 16% of new drugs will be delivered via the respiratory tract for the treatment of both respiratory and non-respiratory diseases. These agents include surfactant, antibiotics, mucokinetics, peptides, anticancer agents, and biologics. Whereas there are excellent nebulizers for the delivery of microgram quantities of many small molecules, efficient and effective aerosol delivery of many of the above agents presents new challenges for aerosol delivery systems. In Phase I, we demonstrated the proof of principal of the components of an aerosol delivery system which addresses the following needs; a) shorter treatment times, b) elimination or at least reduction of the use of excipients c) delivery of fine respirable aerosols without shear-stress-induced molecular degradation d) administration of sparcely soluble agents and e) delivery of surfactant. Using this bench model of SUPRAER we generated large aqueous aerosols which following evaporation and concentration were delivered as respirable concentrated dry power aerosols at a concentration of 5 mg/l. This Phase II we will optimize, construct and test an alpha prototype of SUPRAER(tm), which will deliver 2 to 10 times the dose of active agent per breath than current technologies. The resultant dry power aerosol, of 3 ¿m aerodynamic diameter will be delivered at inspiratory flow rates of 20-30 l/min. The alpha prototype will be robust, functional, manufacturable, and have patient friendly features. SUPRAER will be used to generate aerosols of surfactant, tobramycin, insulin and mannitol. The performance and output aerosol characteristics will be compared with competitive marketed products with FDA approval. SUPRAER(tm) will decrease the time required for inhalation therapy as well as broaden the range of therapeutic agents that can be successfully administered via the respiratory tract.

描述（由申请人提供）：据估计，16%的新药将通过呼吸道给药，用于治疗呼吸道和非呼吸道疾病。这些制剂包括表面活性剂、抗生素、粘膜动力学、多肽、抗癌剂和生物制剂。虽然有许多优良的雾化器用于输送微克量的许多小分子，但许多上述试剂的高效和有效的气溶胶输送对气溶胶输送系统提出了新的挑战。在第一阶段，我们展示了气溶胶输送系统组件的主要证明，该系统可满足以下需求；A)更短的治疗时间；b)消除或至少减少辅料的使用；c)输送无剪切应力诱导的分子降解的可吸入气溶胶；d)施用难溶剂；e)输送表面活性剂。使用SUPRAER的实验模型，我们生成了大的水性气溶胶，经过蒸发和浓缩后，以浓度为5mg /l的可吸入浓缩干动力气溶胶的形式输送。在第二阶段，我们将优化、构建和测试SUPRAER（tm）的alpha原型，它将比现有技术提供2到10倍的每次呼吸的活性剂剂量。由此产生的干动力气溶胶，空气动力学直径为3¿m，将以20-30升/分钟的吸气流速输送。alpha原型将是健壮的，功能齐全的，可制造的，并具有病人友好的特点。SUPRAER将用于生产表面活性剂、妥布霉素、胰岛素和甘露醇的气雾剂。性能和输出气溶胶特性将与FDA批准的市场竞争产品进行比较。SUPRAER（tm）将减少吸入治疗所需的时间，并扩大可通过呼吸道成功给药的治疗剂的范围。