Formulation Development Core

配方开发核心(核心C)的总体目标是提供配方前数据， 支持项目1、2和3的配方开发工作和配方评估评估。 此外，核心将协调和监督所有GMP的制造、发布和稳定性评估 在项目3中拟议的临床试验中使用的用品。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和与生物相关的方法 直肠杀微生物剂产品的评价。鉴于在解剖学和生理学上的显著差异 直肠和阴道室，设计直肠专用杀菌剂产品是必要的，以有效地 抑制艾滋病毒的直肠传播。核心活动范围内的制定战略将侧重于两个 假说以凝胶型半固体剂型或灌肠型液体剂型为中心。量化 实验室已经开发出针对UC781和TFV的检测方法。这些化验方法将用于 在整个开发过程中。一旦原型配方被开发出来，它们将被 在项目1中对毒性和生物活性进行了评估。此数据将用于选择最佳产品 进步。将扩大最佳产品的规模，并制造高质量的研发材料用于分析 项目2中的老鼠功效模型。核心将持续监控产品的机械和化学 在整个开发过程中具有独特的特点。将实现GMP质量材料的制造 通过在GMP质量半固态生产方面拥有丰富经验的合同研究实验室 系统。核心将负责批次记录的方法转移、开发和签字 协助制定为GMP产品建立的产品评估方法的协议 放行，监督GMP批次生产，审查获得的稳定性结果。三个GMP批次将是 制造(仅限UC781、仅限TFV和组合)。来自核心的另一个重要结果将是 目前直肠产品的生物相关产品评估的发展 缺乏这样的方法。核心将直接支持该赠款提案的项目1、2和3。

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.