Formulation Development Core

配方开发核心

• 批准号: 7681954
• 负责人: Lisa Cencia Rohan
• 金额: $ 30.47万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-23 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7681954
• 关键词: AIDS prevention; Anti-Retroviral Agents; Anus; Applications Grants; Biological Assay; Characteristics; Chemicals; Clinical; Clinical Research; Clinical Trials; Colon; Data; Development; Distal; Dosage Forms; Drug Compounding; Drug Formulations; Evaluation; Excipients; Exposure to; Gel; Goals; HIV; HIV Infections; Human; In Vitro; Informatics; Laboratories; Lead; Lipids; Liquid substance; Local Microbicides; Manufactured Materials; Mechanics; Methods; Modeling; Monitor; Mus; Outcome; Patients; Pharmaceutical Preparations; Phase; Physiological; Placebos; Preparation; Process; Records; Rectum; Research Contracts; Reverse Transcriptase Inhibitors; Safety; Site; Solubility; Solutions; Staging; Surface; Suspension substance; Suspensions; System; Tenofovir; Testing; Tissues; Toxic effect; UC 781; Universities; Vagina; Vaginal delivery procedure; Viscosity; Water; absorption; aqueous; base; chemical property; chemical stability; clinical material; design; drug distribution; enema administration; experience; improved; microbicide; physical property; preclinical evaluation; prevent; programs; protocol development; prototype; rectal; rectal microbicide; research and development; research clinical testing; scale up; success; transmission process

The overall goal of the Formulation Development Core (Core C) is to provide preformulation data, formulation development efforts, and formulation assessment evaluations in support of Projects 1, 2, and 3. In addition the Core will coordinate and oversee manufacture, release, and stability assessment of all GMP supplies to be used in the proposed clinical trials in Project 3. Finally Core C will develop prototype formulations with alternate combinations identified in Project 1 and biologically relevant methods for assessment of rectal microbicide product. Given the significant anatomical and physiological differences in the rectal and vaginal compartments it is essential to design rectal specific microbicide products to effectively inhibit rectal transmission of HIV. Formulation strategies within the scope of Core activities will focus on two hypothesis centered on gel like semisolid dosage forms or enema like liquid dosage forms. Quantitative assays have been developed in the laboratory for both UC781 and TFV. These assays will be used throughout the development process. Once prototype formulations have been developed they will be evaluated for toxicity and bioactivity in Project 1. This data will be used to choose the optimal products for advancement. The optimal products will be scaled up and R&D quality material manufactured for analysis in the mouse efficacy model in Project 2. The core will continually monitor product mechanical and chemical characteristics throughout the development process. Manufacture of GMP quality material will be achieved through a contract research lab with extensive experience with manufacture of GMP quality semisolid systems. The Core will be responsible for methods transfer, development and sign off of batch records generated, assist in protocol development for product assessment methods established for GMP product release, oversee GMP batch manufacture, and review stability results obtained. Three GMP batches will be manufactured (UC781 only, TFV only, and combination). Another important outcome from the core will be the development of biologically relevant product assessment evaluations for rectal products given the current lack of such methods. The core will directly support Projects 1, 2, and 3 of this grant proposal.

处方开发核心（核心C）的总体目标是提供处方前数据， 制剂开发工作和制剂评估评价，以支持项目1、2和3。 此外，核心将协调和监督所有GMP的生产、放行和稳定性评估 拟用于项目3中拟定临床试验的供应品。最后，Core C将开发原型 具有项目1中确定的替代组合的制剂以及用于 直肠杀微生物剂产品的评估。考虑到在解剖和生理上的显著差异， 直肠和阴道隔室，必须设计直肠特异性杀微生物剂产品， 抑制艾滋病毒直肠传播。核心活动范围内的制定战略将侧重于两个方面： 假设集中于凝胶样半固体剂型或灌肠样液体剂型。定量 已经在实验室中开发了用于UC 781和TFV的测定。这些检测将用于 在整个开发过程中。一旦开发出原型配方， 在项目1中评价毒性和生物活性。这些数据将用于选择最佳产品， 进步。最佳产品将按比例扩大，并研发制造用于分析的优质材料， 项目2中的小鼠功效模型。核心将持续监控产品的机械和化学性能 在整个发展过程中。将实现GMP质量材料的生产 通过一个合同研究实验室，在生产GMP质量半固体方面具有丰富的经验， 系统.核心负责方法转移、开发和批记录的签核 生成，协助为GMP产品建立的产品评估方法的方案开发 放行，监督GMP批次生产，并审查获得的稳定性结果。三个GMP批次将 制造（仅UC781，仅TFV和组合）。核心的另一个重要成果将是 鉴于目前的情况，开发直肠产品的生物学相关产品评估评价 缺乏这样的方法。核心将直接支持本赠款提案的项目1、2和3。