SUPRAER, High Dose Rate Aerosol Drug Delivery

SUPRAER，高剂量率气雾剂药物输送

• 批准号: 7501482
• 负责人: Donovan B Yeates
• 金额: $ 48.92万
• 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 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7501482
• 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输送，用于治疗呼吸道和非呼吸道疾病，这些药物包括表面活性剂、抗生素、粘液动力学、肽、抗癌剂、除了用于输送微克量的许多小分子的优秀雾化器外，上述许多药剂的高效且有效的气雾剂输送对气雾剂提出了新的挑战。在第一阶段，我们证明了气雾剂输送系统的组成部分的原理，该系统满足以下需求：a）更短的治疗时间，b）消除或至少减少赋形剂的使用c）无需输送细小的可吸入气雾剂。剪切应力诱导的分子降解 d) 稀溶剂的施用和 e) 表面活性剂的输送 使用 SUPRAER 的这个实验台模型，我们产生了大的水性气溶胶，其如下。蒸发和浓缩以浓度为 5 mg/l 的可吸入浓缩干粉气雾剂形式提供。 在第二阶段，我们将优化、构建和测试 SUPRAER(tm) 的 alpha 原型，该原型将提供 2 至 10 倍的活性剂量。所产生的干粉气雾量为 3 ¿ m 空气动力学直径将以 20-30 升/分钟的吸气流速输送。 alpha 原型将坚固、实用、可制造，并具有患者友好的特性，将用于产生表面活性剂、妥布霉素、胰岛素和甘露醇的气雾剂。性能和输出气雾剂特性将与 FDA 批准的竞争性市场产品进行比较，这将减少吸入治疗所需的时间。扩大可以通过呼吸道成功给药的治疗药物的范围。